This summary is based on the 3rd edition of Essential Cell Biology from Alberts et al. The first 10 chapters are open access and can be found here: First part of the summary
Cell membranes enable a cell to create barriers that confine particular molecules to specific compartments. The simplest bacteria have only a single membrane, the plasma membrane. Eucaryotic cells, however, contain in addition a profusion of internal membranes that enclose intracellular compartments. All cell membranes are composed of lipids and proteins and share a common general structure. The lipid component consists of many millions of lipid molecules forming a lipid bilayer. This lipid bilayer gives the membrane its basic structure and serves as a permeability barrier.
The lipids in cell membranes combine two very different properties in a single molecule: each lipid has a hydrophilic (‘water-loving’) has and one or two hydrophobic (‘water-hating’) hydrocarbon tails. There are three major classes of membrane lipid molecules:
The most abundant lipids in cell membranes are phospholipids, and the most common type of phosphoslipid in most cell membranes is phosphatidylcholine. Molecules with both hydrophilic and hydrophobic properties are termed amphipathic. This chemical property plays a crucial part in driving these lipid molecules to assemble into bilayers. They assemble spontaneously into bilayers when placed in water, forming closed compartments that reseals of torn.
Amphipathic molecules re subject to two conflicting forces: the hydrophilic head is attracted to water, while the hydrophobic tail shuns water and seeks to aggregate with other hydrophobic molecules. This conflict is resolved by the formation of a lipid bilayer, because the hydrophilic heads face the water at each of the two surfaces of the sheet of molecules and the hydrophobic tails are all shielded from the water and lie next to one another in the interior of this ‘sandwich’. Finally, the phospholipid bilayers spontaneously close in on themselves to form sealed compartments.
The lipid bilayer is fluid, and individual lipid molecules are able to diffuse within their own monolayer; they do not, however, spontaneously flip from one monolayer to the other. The two layers of the lipid bilayer have different lipid compositions, reflecting the different functions of the two faces of a cell membrane.
The fluidity of a cell membrane (the ease with which its lipid molecules move within the plane of the bilayer) is important for membrane function and has to be maintained within certain limits. The fluidity of a bilayer depends on its phospholipid composition and on the nature of the hydrocarbon tails. The closer and more regular the packing of the tails, the more viscous and less fluid the bilayer will be. The two properties length and degree of unsaturation determine how tightly packed the bilayer is.
A shorter chain length reduces the tendency of the hydrocarbon tails to interact with one another and therefore increases the fluidity of the bilayer.
Each double bond in an unsaturated tail (saturated tails have no double bonds) creates a small kink in the hydrocarbon tail that makes it more difficult for the tails to pack against one another. For this reason, lipid bilayers that contain a large proportion of unsaturated hydrocarbon tails are more fluid than those with lower proportions.
In animals, membrane fluidity is modulated by the inclusion of the sterol cholesterol. Cholesterol molecules fill the spaces between neighboring phospholipid molecules left by the kinks in the unsaturated hydrocarbon tails. In this way cholesterol tends to stiffen the bilayer, making it more rigid and less permeable.
Membrane fluidity is important for many reasons:
It enables membrane proteins to diffuse rapidly in the plane of the bilayer and to interact with one another
It permits membrane lipids and proteins to diffuse from sites where they are inserted into the bilayer after their synthesis to other regions of the cell
It allows membranes to fuse with one another and mix their molecules
It ensures that membrane molecules are distributed evenly between daughter cells when a cell divides
Cells adjust their membrane fluidity by modifying the lipid composition of their membranes. Flippases play a role in synthesizing the lipid bilayer.
Although the lipid bilayer provides the basic structure of all cell membranes and serves as a permeability barrier to the molecules on either side of it, most membrane functions are carried out by membrane proteins. Plasma membrane proteins have a variety of functions: first they take care of transportation of nutrients, metabolites, and ions across the lipid bilayer. Some anchor the membrane to macromolecules on either side. Others function as receptors that detect chemical signals in the cell’s environment and relay them to the cell’s interior; and still others work as enzymes to catalyze specific reactions.
Proteins can be associated with the lipid bilayer of a cell membrane in several ways:
Transmembrane: transmembrane proteins extend across the lipid bilayer, usually as one or more a helices but sometimes as a b sheet curved into the form of a barrel
Membrane-associated: some membrane proteins are anchored to the cytosolic surface by an amphipathic a helix
Lipid-linked: membrane proteins that are attached to either side of the bilayer solely by a covalent attachment to a lipid molecule
Protein-attached: many proteins are attached to the membrane only by relatively weak, noncovalent interactions with other membrane proteins
Proteins that are directly attached to membranes can be removed only by disrupting the lipid bilayer detergents. Such proteins are known as integral membrane proteins. The remaining membrane proteins are know as peripheral membrane proteins; they can be released from the membrane by extraction procedures that interface with protein-protein interactions but leave the lipid bilayer intact.
Before an individual protein can be studied in detail, it must be separated from all the other cellular proteins. For most membrane proteins, the first step in this separation process involves solubilizing the membrane with agents that destroy the lipid bilayer by disrupting hydrophobic associations. The most widely used disruptive agents are detergents. Sodium dodecyl sulfate (SDS) and Trition X-100 are two commonly used detergents. The detergent disrupts the lipid bilayer and brings the protein into solution as protein-detergent complexes.
A cell membrane by itself is enormously thin and fragile. Most cell membranes are therefore strengthened and supported by a framework of proteins, attached to the membrane via transmembrane proteins. The shape of the cell and the mechanical properties of the plasma membrane are determined by a meshwork of fibrous proteins, called the cell cortex, which is attached to the cytosolic surface of the membrane.
Many of the proteins and some of the lipids exposed on the surface of cells have attached chains of sugars which help protect and lubricate the cell surface and are involved in cell-cell recognition. Some proteins, called lectins, are specialized to recognize particular oligosaccharide side chains and bind to them.
Although many membrane proteins can diffuse rapidly in the plane of the membrane, cells have ways of confining proteins to specific membrane domains and of immobilizing particular proteins by attaching them to intracellular or extracellular macromolecules.
The lipid bilayer of cell membranes is permeable to small nonpolar molecules such as oxygen and carbon dioxide and to very small polar molecules such as water. It is highly impermeable to most large, water-soluble molecules and all ions. Transfer of nutrients, metabolites, and ions across the plasma membrane and internal cell membranes is carried out by membrane transport proteins. Cell membranes contain a variety of transport proteins, each of which is responsible for transferring a particular type of solute across the membrane. There are two classes of membrane transport proteins:
The basic difference between carrier proteins and channel proteins is the way they discriminate between solutes. A channel protein discriminates mainly on the basis of size and electric charge; if the channel is open, molecules small enough and carrying the appropriate charge can slip through. A carrier protein, on the other hand, allows passage only to solute molecules that fit into a binding site on the protein; it then transfers these molecules across the membrane one at a time by changing its own conformation.
Living cells maintain an internal ion composition that is very different from the ion composition in the fluid around them. Na+ is the most plentiful positively charged ion (cation) outside the cell, while K+ is the most plentiful of all the solutes in a cell’s environment. The high concentration of Na+ outside the cell is balanced by extracellular Cl-. The high concentration of K+ inside is balanced by a variety of negatively charged intracellular ions (anions). This differential distribution of ions inside and outside the cell is controlled in part by the activity of membrane transport proteins, and in part by the permeability characteristics of the lipid bilayer itself.
The electrochemical gradient represents the net driving force on an ion due to its concentration gradient, and a charged solute (an ion) moves spontaneously down its electrochemical gradient. Such movements are called passive transport (or facilitated diffusion), because they need no other driving forces. All channel proteins and many carrier proteins can act as a conduit for such passive transport. In active transport an uncharged solute or an ion is transported against its concentration or electrochemical gradient in an energy-requiring process. This is carried out only by special types of carrier proteins that can harness some energy source to the transport process.
Although the detailed molecular mechanisms that underlie transport are known for only a few carrier proteins, the general principles are well understood. Solutes can cross the membrane by passive and active transport, and carrier proteins are capable of facilitating both types of movement. Carrier proteins bind specific solutes (inorganic ions, small organic molecules, or both) and transfer them across the lipid bilayer by undergoing conformational changes that expose the solute-binding site first on one side of the membrane and then on the other.
Cells carry out active transport in three main ways:
The Na+-K+ pump in the plasma membrane of animal cells is an ATPase that actively transports Na+ out of the cell and K+ in, maintaining the steep Na+ gradient across the plasma membrane that is used to drive other active transport processes and to convey electrical signals. The downhill movement of the first soluble down its gradient provides the energy to drive the uphill transport of the second. The carrier proteins that do this are called coupled transporters. If the transporters moves both solutes in the same direction across the membrane, it is called a symport. If it moves them in opposite directions, it is called an antiport. A carrier protein that ferries only one type of solute across the membrane (and is therefore not a coupled transporter) is called a uniport.
In animal cells an especially important role is played by symports that use they inward flow of Na+ down its steep electrochemical gradient to drive the import of other solutes into the cell. The epithelial cells that line the gut, for example, transfer glucose from the gut across the gut epithelium. In this way animals use the Na+ gradient to take up nutrients.
Furthermore, the Na+-K+ pump helps to maintain the osmotic balance of animal cells. Movement of water from a region of low solute concentration (high water concentration) to a region of high solute concentration (low water concentration) is called osmosis. The driving forces for the water movement is equivalent to a difference in water pressure and is called the osmotic pressure. In the absence of any counter-acting pressure, the osmotic movement of water into a cell will cause it to swell. Such effects are a severe problem for animal cells, which have no rigid external wall to prevent them from swelling. In animal cells the osmotic balance is regulated by the Na-K+- pump, which pumps out the Na+ that leaks in. At the same time, by helping to maintain a membrane potential, the Na+-K+-pump also tends to prevent the entry of Cl-, which is negatively charged.
Other cells cope with their osmotic problems in different ways. Plant cells are prevented from swelling and bursting by their tough cell wall and so can tolerate a large osmotic difference across their plasma membrane. The protozoan avoids swelling by periodically ejecting the water that moves into the cell.
Channel proteins form aqueous pores across the lipid bilayer through which solutes can diffuse. Whereas transport by carrier proteins can be active or passive, transport by channel proteins is always passive. Most channel proteins are selective ion channels that allow inorganic ions of appropriate size and charge to cross the membrane down their electrochemical gradients. Transport through ion channels is al least 1000 times faster than transport through any known carrier protein.
There are more than a hundred types of ion channels and they mainly differ from one another with respect to their ion selectivity (the type of ions they allow to pass) and gating (the conditions that influence their opening and closing). For a voltage-gated channel, the probability of being open is controlled by the membrane potential. For a ligand-gated channel, it is controlled by the binding of some molecules (the ligand) to the channel protein. For a stress-activated channel, opening is controlled by a mechanical force applied to the channel. Even when opened by their specific stimulus, ion channels do not remain continuously open: they flicker randomly between open and closed conformations. An activating stimulus increases the proportion of time the channel spends in the open state.
All cells have an electrical potential difference, or membrane potential, across their plasma membrane. The membrane potential is determined by the unequal distribution of electric charge on the two sides of the plasma membrane and is altered when ions flow through open channels. In most animal cells, K+-selective leak channels hold the resting membrane potential at a negative value, close to the value where the driving force for movement of K+ across the membrane is almost zero.
A simple formula called the Nernst equation expresses the equilibrium quantitatively and makes it possible to calculate the theoretical resting membrane potential if the ratio of internal to external ion concentrations is known.
The fundamental task of a nerve cell (neuron) is to receive, conduct, and transmit signals. No matter what the meaning of the signal a neuron carries the form of the signal is always the same: it consists of changes in the electrical potential across the neuron’s plasma membrane. Neurons are often extremely elongated and the action potentials therefore have to travel long distances along an axon without weakening.
Every neuron consists of a cell body (containing the nucleus); a long axon, which conducts signals away form the cell body toward distant target cells; and dendrites, which extend from the cell body like antennae and provide an enlarged surface area to receive signals from the axons of other neurons. The axon divides at its far end into many branches, each of which ends in a nerve terminal; so that the neuron’s message can be passed simultaneously to many target cells.
Action potentials are usually mediated by voltage-gate Na+ channels that open in response to depolarization of the plasma membrane (a shift in the membrane potential to a less negatively value). Such a depolarization is caused by the action of signaling molecules, called neurotransmitters, released by other neurons. When the voltage-gate Na+ channels are open Na+ enters the cell, depolarizes the membrane further. The membrane potential swings past zero and reaches +40mV before it returns to its resting negatively value, as the action potential terminates. The membrane is helped to return to its resting value by inactivation of the Na+ channels, opening of voltage-gated K+ channels, and through the K+ leak channels.
When the action potential reaches the ends of the axon (the nerve terminals) the signal must be relayed to the target cells that the nerve terminals contact. The signal is transmitted at specialized junctions known as synapses. At most synapses the presynaptic and postsynaptic plasma membranes are separated from each other by a synaptic cleft, which the electrical signal cannot cross. For the message to be transmitted the electrical signal is converted into a chemical signal, known as a neurotransmitter. Neurotransmitters are stored in the nerve terminals, packaged in synaptic vesicles. When the action potential reaches the terminal, voltage-gated Ca2+ channels in nerve terminals couple electrical signals to transmitter release at synapses. Transmitter-gated ion channels convert these chemical signals back into electrical signals in the postsynaptic target cell.
The response produced by a neurotransmitter at a synapse can be either excitatory or inhibitory. Excitatory neurotransmitters, mainly acetylcholine and glutamate, open transmitter-gated channels that are permeable to Na+ and thereby depolarize the postsynaptic cell membrane toward the threshold potential for firing an action potential. Inhibitory neurotransmitters, mainly GABA and glycine, open transmitter-gated Cl- channels and thereby suppress firing by keeping the postsynaptic cell membrane polarized.
Transmitter-gated ion channels are major targets for psychoactive drugs.
As mentioned earlier, cells require a constant supply of energy to generate and maintain the biological order that keeps them alive. Perhaps the most important fuel molecules are the sugars. Plants make their own sugars by photosynthesis, whereas animals obtain sugars by eating other organism. Nevertheless, the process whereby these sugars are oxidized to generate energy is very similar in both animals and plants. Glucose and other food molecules are broken down by controlled stepwise oxidation to provide useful chemical energy in the form of the activated carriers ATP and NADH.
The proteins, lipids and polysaccharides that make up most of the food we eat must be broken down into smaller molecules before our cells can use them; this happens in three stages:
In stage 1 the enzymatic breakdown of food molecules (digestion) occurs either outside the cells in our intestine or in a specialized organelle within cells called lysosome. In either case, digestive enzymes reduce the large polymeric molecules in food into their monomeric subunits (proteins into amino acids and polysaccharides into sugar). After digestion, the small organic molecules derived from the food enter the cytosol of a cell, where their gradual oxidation begins
The most important step of stage 2 is the degradation of glucose, a process called glycolysis. Glycolysis produces ATP without the involvement of molecular oxygen (O2 gas). It occurs in the cytosol of most cells, including many anaerobic microorganisms.
Glycolysis converts each molecule of glucose into two smaller molecules of pyruvate. During this formation two types of activated carrier molecules are produced: ATP and NADH. At the end of glycolysis, there is a net gain of two molecules ATP (4 produced, but 2 consumed during the process) and two molecules of NADH for each glucose molecule broken down. Next the pyruvate passes from the cytosol into mitochondria.
Stage 3 takes place in mitochondria. Here the pyruvate is converted into CO2 plus acetyl coenzyme A (CoA). The acetyl group enters a series of reactions called the citric acid cycle. The citric acid cycle accounts for about two-thirds of the total oxidation of carbon compounds in most cells, and its major products are CO2 and NADH. The CO2 is released as a waste product, while the high-energy electrons from NADH are passed to a membrane-bound electron-transport chain, eventually combining with O2 to produce H2O. Each turn of the citric acid cycle produces one molecule of GTP and one molecule of FADH2. The energy that is stored in the high-electrons of NADH and FADH2 will be used to drive a process that produces ATP and consumes molecular oxygen (O2). It is in these final steps that most of the energy released by oxidation is harnessed to produce most of the cell’s ATP. Because the energy for it ultimately derives from the oxidative breakdown of food molecules, the phosphorylation of ADP to form ATP in the mitochondrial inner membrane is known as oxidative phosphorylation.
As mentioned above, sugars are broken down by distinct sets of reactions: glycolysis (which occurs in the cytosol), the citric acid cycle (in the mitochondrial matrix), and oxidative phosphorylation (in the inner mitochondrial membrane). In total, the complete oxidation of a molecule of glucose to H20 and CO2 produces about 30 molecules of ATP (in contrast to glycolysis alone, which produces 2 molecules of ATP). Besides sugars, another major energy source in foods is fat. The fatty acids produced from fats are imported into mitochondria and converted to acetyl CoA molecules. These acetyl CoA molecules are then further oxidized through the citric acid cycle, producing NADH and FADH2, just like the acetyl CoA derived from pyruvate.
For most animal and plant cells, glycolysis is just a prelude to the final stage of the breakdown of food molecules. But for many anaerobic organisms, which do not use molecular oxygen and can grow and dived in its absence, glycolysis is the principle source of the cell’s ATP. In these anaerobic conditions, the pyruvate and the NADH electrons stay in the cytosol. The pyruvate is converted into products that are excreted from the cell, like for example lactate and ethanol. The NADH is converted back into NAD+; this is required to maintain the reactions of glycolysis.
Cells store food molecules in special reservoirs. Glucose subunits are stored as glycogen in animals and as starch in plants; both animals and plants store food as fats. The food reservoirs produced by plants are the major sources of food for animals, including humans.
Molecules ingested as food are used not only as sources of metabolic energy but also as raw material for biosynthesis. Thus many intermediates of glycolysis and the citric acid cycle are starting points for pathways that lead to the synthesis of proteins, nucleic acids, and the many other specialized molecules of the cell.
The thousands of different reactions carried out simultaneously by a cell are closely coordinated, enabling the cell to adapt and continue to function under a wide range of external conditions.
The main energy currency in cells is ATP. In eukaryotic cells, small amounts of ATP are generated during glycolysis in the cytosol, but most ATP is produced by membrane-based processes in the mitochondria, using energy derived from oxidation of sugars and fatty acids. Similar processes also occur in the cell membrane of many bacteria. The mechanism for making ATP consists of two linked stages, both of which are carried out by protein complexes embedded in a membrane:
Stage 1: electrons derived from the oxidation of food molecules are transferred along an electron-transport chain, which is embedded in the membrane. These electron transfers release energy that is used to pump protons (H+) across the membrane and thus generate an electron chemical proton gradient. This gradient is a form of stored energy that can be used when the ions flow back down their electrochemical gradient.
Stage 2: H+ flows back down its electrochemical gradient through a protein complex called ATP synthase, which catalyzes the energy-requiring synthesis of ATP from ADP and inorganic phosphate (Pi).
The linkage of electron transport, proton pumping, and ATP synthesis is called chemiosmotic coupling. Chemiosmotic coupling first evolved in bacteria. Therefore, it is perhaps not surprising that aerobic eucaryotic cells appear to have adopted the bacterial chemiosmotic mechanisms by engulfing aerobic bacteria to form mitochondria and cyanobacteria to form chloroplasts.
Mitochondria are present in nearly all eucaryotic cells and contain their own DNA and RNA, and a complete transcription and translation system including ribosomes, which allows them to synthesize some of their own proteins. Defects in mitochondrial function can have serious repercussions for an organism. An inherited disorder called myoclonic epilepsy and ragged red fiber disease (MERRF) caused by a mutation in one of the mitochondrial transfer RNA genes, is characterized by a decrease in synthesis of the mitochondrial proteins required for electron transport and ATP production. As a result, patients with this disorder typically experience muscle weakness or hart problems (from the effect on cardiac muscle) and epilepsy or dementia (from the effects on nerve cells). Muscle and nervous tissue suffer most when mitochondria are defective because they need particularly large amounts of ATP to function optimally.
Mitochondria are enclosed by two concentric membranes. The outer and inner mitochondrial membranes create two mitochondrial compartments: a large internal space called the matrix and the intermembrane space. The matrix is a large internal space that contain a mixture of hundreds of enzymes, and it contains several identical copies of the mitochondrial DNA genome. The inner mitochondrial membrane is folded into numerous cristae, which greatly increase its total surface area. An electrochemical gradient of H+, which drives the ATP synthase, is established across this membrane. The inner membrane contains proteins with three types of function:
The outer membrane contains many molecules of a transport protein called porin, which forms wide aqueous channels through the lipids bilayer. As a result, the outer membrane is permeable to all molecules of 5000 dalton or less. Other proteins in this membrane include enzymes involved in mitochondrial lipid synthesis and enzymes that convert lipid substrates into forms that are subsequently metabolized in the matrix.
Mitochondria can use both pyruvate and fatty acids as fuel. Pyruvate comes mainly from glucose and other sugars, and fatty acids come from fats. Pyruvate and fatty acids enter the mitochondrium and are converted into acetyl CoA. Then they are further metabolized by the citric acid cycle, which reduces NAD+ to NADH, and FAD to FADH2. In the process of oxidative phosphorylation, high-energy electrons from NADH and FADH2 are then passed along the electron-transport chain (the respiratory chain) in the inner membrane to oxygen. Much of the energy released by electron transfers along the respiratory chain is harnessed to pump H+ out of the matrix, thereby creating a transmembrane electrochemical proton (H+) gradient. The proton pumping is carried out by three large respiratory enzyme complexes embedded in the membrane. Each complex includes transmembrane proteins that hold the entire protein complex firmly in the inner mitochondrial membrane. The three respiratory enzyme complexes are:
The resulting electrochemical proton gradient across the inner mitochondrial membrane is used to drive the ATP synthesis in the process of oxidative phosphorylation. The device that makes this possible is a large membrane-bound enzyme called ATP synthase. This enzyme creates a hydrophilic pathway across the inner mitochondrial membrane that allows protons to flow down their electrochemical gradient. ATP synthase is a reversible coupling device. It can either harness the flow of protons down their electrochemical gradient to make ATP or use the energy of ATP hydrolysis to pump protons across a membrane, like H+ pumps. Whether the ATP synthase primarily makes or consumes ATP depends on the magnitude of the electrochemical proton gradient across the membrane in which it sits.
The synthesis of ATP is not the only process driven by the electrochemical proton gradient. The electrochemical gradient also drives the active transport of metabolites into and out the mitochondrion, or coupled transport processes.
In plants, photosynthesis is carried out in a specialized intracellular organelle, the chloroplast. Chloroplasts perform photosynthesis during daylight hours and thereby produce ATP and NADPH, which in turn are used to convert CO2 into sugars inside the chloroplast. The sugars are then used to make ATP and as starting materials for many of the other organic molecules that the plant cell needs. Chloroplasts have a highly permeable outer membrane, a much less permeable inner membrane (in which membrane transport proteins are embedded) and a narrow intermembrane space in between. Together these membranes form the chloroplast envelope. The inner membrane surrounds a large space called the stroma, which is analogous to the mitochondrial matrix and contains many metabolic enzymes. Like the mitochondrium, the chloroplast evolved from an engulfed bacterium, and it still contains its own genome and genetic system. There is, however, an important difference between the organization of mitochondria and that of chloroplasts. Compared with mitochondria, chloroplasts are larger and have an extra compartment. A chloroplast contains, in addition to an inner and outer membrane, a thylakoid membrane enclosing a thylakoid space. The thylakoid membrane contains the light-capturing systems, the electron-transport chains and ATP synthase.
The many reactions that occur during photosynthesis in plants can be grouped into two broad categories:
Photosynthetic electron-transfer reactions (also called the ‘light-reactions’): in this reactions is water oxidized and oxygen released
Carbon-fixation reactions (also called the ‘dark reactions’): in this reactions, which begin in the chloroplast stroma and continue in the cytosol, carbon dioxide is assimilated (fixed) to produce sugars and a variety of other organic molecules
In photosynthesis high-energy electrons are generated when sunlight is absorbed by chlorophyll; this energy is captured by protein complexes known as photosystems, which are located in the thylakoid membranes of chloroplasts.
Electron-transport chains associated with photosystems transfer electrons from water to NADP+ to form NADPH, with the concomitant production of an electrochemical proton gradient across the thylakoid membrane. Molecular oxygen is generated as a by-product. As is mitochondria, the proton gradient across the thylakoid membrane is used by an ATP synthase embedded in the membrane to generate ATP. The ATP and the NADPH made by photosynthesis are used within the chloroplast to drive the carbon-fixation cycle in the chloroplast stroma, thereby producing carbohydrate from CO2. Carbohydrate is exported to the cell cytosol, where it is metabolized to provide organic carbon, ATP (mostly via mitochondria), and reducing power for the rest of the cell.
Both mitochondria and chloroplasts are thought to have evolved from bacteria that were endocytosed by primitive eukaryotic cells. Each retains its own genome and divides by processes that resemble a bacterial cell division. Because mitochondria and chloroplasts have component proteins that are encoded by two separate genetic systems, their growth and proliferation is complicated.
Chemiosmotic coupling mechanisms are widespread and of ancient origin. Modern microorganisms that live in environments similar to those thought to have been present on the early Earth also use chemiosmotic coupling to produce ATP.
Whereas a prokaryotic cell consists of a single compartment, the cytosol, enclosed by the plasma membrane, a eukaryotic cell is subdivides by internal membranes. These membranes create enclosed comportments in which sets of enzymes can operate without interference from reactions occurring in other compartments. They major membrane-enclosed organelles are:
Nucleus: this is generally the most prominent organelle in eukaryotic cells. It is surrounded by a double membrane, known as the nuclear envelope, and communicates with the cytosol via nuclear pores that perforate the envelope.
Endoplasmatic reticulum (ER): a system of interconnected sacs and tubes of membrane that often extends throughout most of the cell. The ER is the major site of new-membrane synthesis in the cell. Large areas of the system have ribosomes attached to the cytosolic surface and are called rough ER. The ribosomes are synthesizing proteins that are delivered into the ER lumen or ER membrane. The smooth ER is the site of steroid hormone synthesis and the site where a variety of organic molecules (including alcohol) are detoxified.
Golgi apparatus: receives proteins and lipids from the ER, modifies them, and then dispatches them to other destinations in the cell.
Lysosomes: small sacs of digestive enzymes that degrade worn-out organelles, as well as macromolecules and particles taken into the cell by endocytosis.
Endosomes: sort the ingested molecules and recycle some back to the plasma membrane.
Mitochondria: their main function is ATP synthesis by oxidative phosphorylation
Chloroplasts (in plant cells): by photosynthesis they produce ATP and carbon fixation
Peroxisomes: they contain enzymes that break down lipids and destroy toxic molecules.
Much can be learned about the composition and function of an organelle once it has been isolated from other cell structures; organelles are isolated by differential centrifugation. Many of the membrane-enclosed organelles, including the ER, Golgi apparatus, mitochondria, and chloroplasts, are held in their relative locations in the cell by attachment to the cytoskeleton, especially to microtubules.
To understand the relationship between the different compartments of a modern eukaryotic cell, it is useful to consider how they might have evolved. The precursors of the first eukaryotic cells are thought to have been simple microorganisms, which had a plasma membrane but no internal membranes. The plasma membrane in such cells would have provided all membrane-dependent functions, as does a plasma membrane in most bacteria. Membrane-enclosed organelles are thought to have arisen in evolution in at least two ways:
The nuclear membrane and the membranes of the ER, Golgi apparatus, endosomes, and lysosomes are believed to have originated by invagination of the plasma membrane. These membranes, and the organelles they enclose, are all part of what is called the endomembrane system.
Mitochondria and chloroplasts differ from all other organelles in that they possess their own small genomes and can make some of their own proteins. The similarity of these genomes to those of bacteria suggests that mitochondria and chloroplasts evolved from bacteria that were engulfed by primitive eukaryotic cells with which they initially lived in symbiosis. This would also explain why these organelles are enclosed by two membranes.
Before a eukaryotic cell reproduces by dividing in two, it has to duplicates its membrane-enclosed organelles. As a cell grows, membrane-enclosed organelles enlarge by incorporation of new molecules. The organelles then divide and at cell division they are distributed between the two daughter cells. The nuclear envelope, ER and Golgi apparatus break up into small vesicles, which ten coalesce again as the two daughter cells are formed. Organelle growth requires a supply of new lipids to make more membrane and a supply of the appropriate proteins. These newly synthesized proteins must be accurately delivered to organelles.
The synthesis of all proteins in the cell begins of ribosomes in the cytosol. The exceptions are the few mitochondrial and chloroplasts proteins that are synthesized on ribosomes inside these organelles. However, most mitochondrial and chloroplasts proteins are made in the cytosol. The fate of any protein molecule synthesized in the cytosol depends on its amino acid sequence, which can contain a sorting signal that directs the protein to the organelle in which it is required. Proteins that lack such signals remain as permanent residents in the cytosol. The typical sorting signal on proteins is a stretch of amino acids sequence, 15-60 amino acids long. This signal sequence is often removed from the finished protein once the sorting decision has been executed.
Proteins are imported into the organelles by three mechanisms:
Nuclear proteins contain nuclear localization signals that help direct their active transport from the cytosol into the nucleus through nuclear pores, which penetrate the double-membrane nuclear envelope. First, specialized proteins, called nuclear transport receptors, bind to the prospective nuclear protein. The resulting complex is guided to a nuclear pore by fibrils at extend from the pore into the cytosol. The binding of the nuclear proteins to the pore, opens the pore, and the complex is actively transported into the nucleus by a process that uses the energy provided by GTP hydrolysis. The receptors are then exported back through the pores into the cytosol for reuse. Proteins can enter the nucleus without being unfolded.
Most mitochondrial and chloroplast proteins are made in the cytosol and are then actively transported into the organelles by protein translocators in their membranes. Proteins must be unfolded to allow them to snake through the chloroplast or mitochondrial membrane. Chaperone proteins inside the organelles help to pull the proteins across the two membranes and to refold the protein once it is inside. Subsequent transport to a particular site within the organelle usually requires further sorting signals in the protein, which are often only exposed after the first signal sequence in removed. Proteins moving from cytosol into the ER also use the mechanism of protein translocators.
Proteins moving from the ER onward and from one compartment of the endomembrane system to another are transported by transport vesicles.
The outer nuclear membrane is continuous with the ER. The ER is the membrane factory of the cell; it makes most of the cell’s lipids and many of its proteins. The proteins are made by ribosomes bound to the surface of the rough ER. There are two separate populations of ribosomes in the cytosol. Membrane-bound ribosomes are attached to the cytosolic side of the ER membrane and are making proteins that are being translocated into the ER. Free ribosomes are unattached to any membrane and are making al of the other proteins encoded by nuclear DNA.
Ribosomes in the cytosol are directed to the ER if the protein they are making has an ER signal sequence, which is recognized by a signal-recognition particle (SRP) in the cytosol; the binding of the ribosome-SRP complex to a receptor on the ER membrane initiates the translocation process that threads the growing polypeptide across the ER membrane through a translocation channel. Soluble proteins destined for secretion or the lumen of an organelle pass completely into the ER lumen, while transmembrane proteins destined for the ER membrane or other cell membrane remain anchored in the lipid bilayer by one or more membrane-spanning a helices.
In the ER lumen, proteins fold up, assemble with other proteins, form disulfide bonds, and become decorated with oligosaccharide chains. Exit from the ER is an important quality-control step; proteins that either fail to fold properly or fail to assemble with their normal partners are retained in the ER and are eventually degraded.
Protein transport from the ER to the Golgi apparatus and from the Golgi apparatus to other destinations is mediated by transport vesicles that continually bud off from one membrane and fuse with another, a process called vesicular transport.
The vesicular traffic between membrane-enclosed compartments of the endomembrane system is highly organized. In the outward secretory pathway protein molecules are transported from the ER, through the Golgi apparatus, to the plasma membrane or lysosomes. In the inward endocytic pathway extracellular molecules are ingested in vesicles derived from the plasma membrane and are delivered to early endosomes and then to lysosomes.
Vesicles that bud from membranes usually have a distinctive protein coat on their cytosolic surface and are therefore called coated vesicles. After budding from its parent organelle, the vesicle sheds it coat, allowing its membrane to interact directly with the membrane to which it will fuse. Cells produce several kinds of coated vesicles, each with a distinctive protein coat; the assembly of the coat drives the budding process, and the coat proteins help incorporate receptors with their bound cargo molecules into the forming vesicle.
Best-studied vesicles are those that have coats made of the protein clathrin. These clathrin-coated vesicles bud from the Golgi apparatus on the outward secretory pathway and from the plasma membrane on the inward endocytic pathway. Clathrin molecules form basketlike cages that help shape membranes into vesicles. Clathrin itself plays no part in capturing specific molecules for transport. This is the function of a second class of coat proteins called adaptins, which both secure the clathrin coat to the vesicle membrane and help select cargo molecules for transport. Molecules for onward transport carry specific transport signals that are recognized by cargo receptors in the compartment membrane. Adaptins help capture specific cargo molecules by trapping the cargo receptors that bind them. In this way a selected set of cargo molecules, bound to their specific receptors, is incorporated into the lumen of each newly formed cathrin-coated vesicle.
Coated vesicles lose their protein coat soon after pinching off, enabling them to dock and fuse with a particular target membrane. Docking and fusion are thought to be mediated by proteins on the vesicle and on the target membranes, called v-SNAREs and t-SNAREs, respectively. Each organelle and each type of transport vesicle is believed to carry a unique SNARE, and the interactions between complementary SNAREs help ensure that transport vesicles fuse only with the correct membrane. Fusion not only delivers the contents of the vesicle into the interior of the target organelle, it also adds the vesicle membrane to the membrane of the organelle. Pairing of v-SNAREs and t-SNAREs forces the two lipid bilayers into close apposition. Lipids then flow between the two bilayers and the membranes fuse.
The Golgi apparatus receives newly made proteins from the ER; it modifies their oligosaccharides, sort proteins, and dispatches them from the trans Golgi network to the plasma membrane, lysosomes, or secretory vesicles. Some proteins are destined to function in the ER and they are retained in the ER by a C-terminal sequence of four amino acids called an ‘ER retention signal’, which is recognized by a membrane-bound receptor protein in the ER and Golgi apparatus. However, most proteins that enter the ER are destined for other locations. As mentioned above, exit from the ER is highly selective; chaperones prevent misfolded or partially assembled proteins from leaving the ER.
The mutation that causes the genetic disease cystic fibrosis, which causes severe degeneration of the lung, produces a plasma-membrane transport protein that is slightly misfolded. The devastating disease results not because the mutation inactivates an important protein, but because the active protein is discharged by the cell before it is given an opportunity to function.
After the exit from the ER, proteins are further modified and sorted in the Golgi apparatus. The Golgi apparatus consists of a collection of flattened, membrane-enclosed sacs (cisternae). Each Golgi stack has two distinct faces: an entry (or cis) fase and an exit (or trans) face. The cis face is adjacent to the ER, while the trans face points toward the plasma membrane. Soluble proteins and membrane enter the cis Golgi network via transport vesicles derived from the ER. The proteins travel through the cisternae in sequence by means of transport vesicles that bud from one cisterna and fuse with the next. Proteins exit from the trans Golgi network in transport vesicles destined for either the cell surface or another compartment. Both the cis and trans Golgi network are thought to be important for protein soring.
In all eukaryotic cells, transport vesicles continually bud from the trans Golgi network and fuse with the plasma membrane, a process called constitutive exocytosis; the process delivers plasma membrane lipids and proteins to the cell surface and also releases molecules from the cell, a process called secretion. In addition to the constitutive exocytosis pathway, which operated continually, there is also a regulated exocytosis pathway, which operates only in cells that are specialized for secretion. Specialized secretory cells produce large quantities of particular products, such as hormones or digestive enzymes, which are stored in secretory vesicles for later release. These vesicles bud off from the trans Golgi network and accumulate near the plasma membrane. There they wait for the extracellular signal that will stimulate them to fuse with the plasma membrane and release their contents to the cell exterior.
Endocytic pathway
Cells ingest fluid, molecules, and sometimes even particles, by endocytosis, in which regions of plasma membrane invaginate and pinch off to form endocytic vesicles. Two main types of endocytosis are distinguished on the basis of the size of the endocytic vesicles formed:
Pinocytosis (‘cellular drinking’): this involves the ingestion of fluid and molecules via small vesicles (<150 nm in diameter)
Phagocytosis (‘cellular eating’): this involves the ingestion of large particles, such as microorganisms and cell debris, via large vesicles called phagosomes (>250 nm in diameter)
Whereas all eukaryotic cells are continually ingesting fluid and molecules by pinocytosis, large particles are ingested mainly by specialized phagocytic cells. Phagocytic cells ingest large particles by taking them up into phagosomes; these phagosomes then fuse with lysosomes. Phagocytosis is important for digesting food molecules and defense against infections by ingesting invading microorganisms. Because during pinocytosis, a cell’s total surface area and volume remain unchanged, it is clear that as much membrane is being added to the cell surface by vesicle fusion (exocytosis) as is being removed by endocytosis.
Much of the material that is endocytosed is delivered to endosomes and then to lysosomes, where hydrolytic enzymes degrade it; most of the components of the endocytic vesicle membrane, however, are recycled in transport vesicles back to the plasma membrane for reuse.
Cells in multicellular organisms communicate through a large variety of extracellular chemical signals. And communication involves converting information signals from one form to another, a process called signal transduction. In a typical communication between cells, the signaling cell produces a particular type of signal molecule that is detected by the target cell. The target cells possess receptor proteins that recognized and respond specifically to the signal molecule. Signal transduction begins when the receptor protein on the target cell receives an incoming extracellular signal and converts it to the intracellular signals that alter cell behavior.
Single cells and cells in multicellular organisms use a variety of extracellular molecules to send signals to one another:
Endocrine signals: hormones produced in endocrine glands are secreted into the bloodstream and are often distributed widely throughout the body
Paracrine signals: the signaling molecules diffuse locally through the extracellular medium, remaining in the neighborhood of the cell that secretes them. Thus they act as local mediators on nearby cells.
Neuronal signals: neurons can deliver messages across long distances, but in the case of neuronal signaling the message is not broadcast widely but is transmitted quickly along axons to remote target cells.
Contact-dependent signals: this style of signaling does not require the release of a secreted molecule. Instead, the cells make direct contact through signaling molecules lodged in their plasma membranes. The message is delivered when a signal molecule anchored in the plasma membrane of the signaling cell binds to a receptor molecule embedded in the plasma membrane of the target cell.
Many of the signal molecules that regulate inflammation at the site of an infection or control cell proliferation in a healing wound function as paracrine signals. In embryonic development contact-dependent signaling plays an important role; for example it controls nerve-cell production.
A cell in a multicellular organism is exposed to hundreds of different signal molecules in its environment. Each cell must respond selectively to this mixture of signals, disregarding some and reacting to others, according to the cell’s specialized function. Whether a cell responds to a signal molecule depends first on whether is possesses a receptor for that signal. But one signal can still be used to control the behavior of the cell in complex ways:
One signal, binding to one type of receptor protein, can cause a multitude of effect in the same target cell. Furthermore, different types of cells respond to the same signal in different ways.
A cell possesses a collection of different receptors. Such variety makes the cell sensitive to many extracellular signals. These signal molecules work in combinations to regulate the behavior of the cell.
Cells are stimulated by an extracellular signal molecule when it binds to and activates a receptor protein. Each receptor protein recognizes a particular signal molecule. Receptor proteins act as transducers, converting signals from one physical form to another. However, most extracellular signal molecules cannot pass through the plasma membrane; first they must bind to cell-surface receptor proteins that transduce the extracellular signal into different intracellular signals.
Extracellular signal molecules fall into two classes:
Signal molecules that are too large are too hydrophilic to cross the plasma membrane of the target cell. They bind on receptors on the surface of the target cell to relay their message across the membrane.
Signal molecules that are small enough or hydrophobic enough to slip easily through the plasma membrane. Once inside, these signal molecules either activate intracellular enzymes or bind to intracellular receptor proteins that regulate gene expression. Steroid hormones (including cortisol and testosterone) and nitric oxide (NO) are examples of small hydrophobic extracellular signal molecules. Acetylcholine released by nerve terminals in the blood-vessel wall stimulates endothelial cells lining the blood vessel to make and release NO. The NO diffuses out of the endothelial cells and into adjacent smooth muscle cells, causing them to relax.
In contrast to NO and the steroid hormones, the majority of signal molecules are too large or hydrophilic to cross the plasma membrane of the target. These signal molecules bind to receptor proteins on the target cell surface:
There are three main classes of cell-surface receptors:
Ion-channel-linked receptors: this receptor opens in response to binding of its signal molecule. The result is a flow of ions across the membrane, which produces an electrical current
G-protein-linked receptors: when a G-protein-linked receptor binds its extracellular signal molecule, the signal is passes first to a GTP-binding protein (a G-protein) that is associated with the receptor. The activated G-protein then leaves the receptor and turns on a target enzyme in the plasma membrane
Enzyme-linked receptors: when binding of the signal molecule activates this receptor, enzyme activity is switched on at the other end of the receptor, which is inside the cell
In sum, G-protein-linked receptors and enzyme-linked receptors respond to extracellular signals by initiating cascades of intracellular signaling reactions that alter the behavior of the cell.
G-protein-linked receptors form the largest family of cell-surface receptors. They mediate responses to an enormous diversity of extracellular signal molecules. These signal molecules are as varied in structure as they are in function. Despite the diversity of the signal molecules that bind to them, all G-protein-linked receptors possess a similar structure: each is made of a single polypeptide chain that threads back and forth across the lipid bilayer seven times. There are also several varieties of G proteins. All of these G proteins, however, have a similar general structure and operate in a similar way. All G proteins are composed of three protein subunits: the a, b and g subunits.
In the unstimulated state, the a subunit has GDP bound to it, and the G protein is purposeless. When an extracellular ligand binds to its receptor, the altered receptor activates a G protein by causing the a subunit to lose some of its affinity for GDP, which it exchanges for a molecule of GTP. This activation breaks up the G protein subunits: the switched-on a subunit detaches from the bg complex, giving rise to two separate molecules that now roam independently along the plasma membrane. The amount of time that the a- and bg subunits remain dissociated is limited by the behavior of the a subunit. The a subunit has an intrinsic GTP-hydrolyzing (GTPase) activity, and it eventually hydrolyzes its bound GTP back to GDP; the a subunit then reassociates with the bg complex. The reconstituted G protein is now ready to be reactivated by another activated receptor.
In concluding, when an extracellular signal molecule binds to a seven-pass transmembrane receptor, the receptor protein undergoes a conformational change that enables it to activate a G protein located on the underside of the plasma membrane. These G-proteins act as molecular switches, transmitting the signal onward for a short period and then switching themselves off by hydrolysis their bound GTP and GDP. This system demonstrates that the mechanisms that shut a signal off are as important as the mechanisms that turn it on. The disease cholera is caused by a bacterium that multiplies in the intestine where it produces a protein called cholera toxin. This protein enters the cells that line the intestine and modifies the a subunit of a G-protein in such way that it can no longer hydrolyze its bound GTP. The altered a subunit thus remains in the active state, continuously transmitting a signal to its target proteins. In intestinal cells, this causes a prolonged and excessive outflow of Cl- and water into the gut, resulting in catastrophic diarrhea and dehydration.
As mentioned above, there are many different G proteins:
Some G proteins directly regulate ion channels in the plasma membrane. For example, G proteins couple receptor activation to the opening of K+ channels in the plasma membrane of heart muscle cells.
Other G proteins activate membrane-bound enzymes. The most frequent target enzymes for G proteins are adenylyl cyclase, the enzyme responsible for production of the signaling molecule cyclic AMP, and phospholipase C, which generates the messenger molecules inositol trisphosphate (IP3) and diacylglycerol.
We take a closer look to G proteins that activate membrane-bound enzymes. Adenylyl cyclase and phospholipase C are activated by different types of G proteins, so that cells are able to couple production of the signaling molecules to different extracellular signals. Many extracellular signals acting via G protein-linked receptors affect the activity of adenyl cyclase. Most commonly, the activated G protein a subunit switches on the adenyl cyclase, causing an increase in the synthesis of cyclic AMP from ATP. To help eliminate the signal, a second enzyme, called cyclic AMP phoshodiesterase, converts cyclic AMP to ordinary AMP. Cyclic AMP exerts various effects by activating the enzyme protein kinase A (PKA). This enzyme is normally held inactive in a complex with another protein. The binding of cyclic AMP forces a conformational change that unleashes the active kinase. In some cases the effects of activating a cyclic AMP cascade are rapid; in others the effects are slow. A rise in intracellular cyclic AMP can activate gene transcription.
The inositol phospolipid pathway begins with the activation of the membrane-bound enzyme phospholipase C. This enzyme activates two signaling pathways: IP3 and diacylglycerol. IP3 opens ion channels in the membrane of the endoplasmatic reticulum, releasing a flood of free Ca2+ ions into the cytosol. Ca2+ itself acts as an intracellular messenger, altering the activity of a wide range of proteins. Together with this Ca2+, diacylglycerol helps recruit and activate an enzyme called protein kinase C (PKC).
In concluding, a rise in cyclic AMP activates protein kinase A (PKA), while CA2+ and diacylglycerol in combination activate protein kinase C (PKC). PKA and PKC phosphorylate secreted target proteins on serines and threonines, thereby altering protein activity. Different cell types contain different sets of target proteins and are affected in different ways.
In general, stimulation of G-proteins-linked receptors produces rapid and reversible cell responses!
Plants, like animals use enzyme-linked cell-surface receptors to control their growth and development. Like G-protein-linked receptors, enzyme-linked receptors are transmembrane proteins that display their ligand-binding domains on the outer surface of the plasma membrane. Instead of associating with a G protein, the cytoplasmatic domain of the receptor acts as an enzyme or forms a complex with another protein that acts as an enzyme. Most are receptor tyrosine kinase, which phosphorylate tyrosines on selected intracellular proteins. Activated receptor tyrosine kinases cause the assembly of an intracellular signaling complex on the intracellular tail of the receptor. A part of this complex serves to activate Ras, a small GTP-binding protein, which activates a cascade of protein kinases that relay the signal from the plasma membrane to the nucleus. This cascade is called a MAP-kinase cascade.
MAP-kinase is the final kinase in the chain and it phosphorylates certain gene regulatory proteins on serines and threonines, altering their ability to control gene transcription and thereby causing a change in the pattern of gene expression. This shift may stimulate cell proliferation, cell survival or induce cell differentiation. However, mutations that stimulate cell proliferation by making Ras constantly active are a common feature of many cancers.
Some enzyme-linked receptors activate a direct pathway to the nucleus. Instead of activating signaling cascades, they turn on gene regulatory proteins right at the plasma membrane. Unlike the receptor tyrosine kinases that stimulate signaling cascades, cytokine receptors have no intrinsic enzyme activity. Instead, they are associated with cytoplasmatic tyrosine kinases called JAKs that are activated when a cytokine binds to its receptor. Once activated, the JAKs phosphorylate and activate cytoplasmatic gene regulatory proteins called STATs, which then migrates to the nucleus, where they stimulate transcription of specific target genes.
An even more direct signaling pathway is used by the TGF-b receptors, which activate gene regulatory proteins directly at the plasma membrane.
Different intracellular signaling pathways interact, enabling cells to produce an appropriate response to a complex combination of signals. Some combinations of signals will cause it to proliferate; and in the absence of any signals, most cells will kill themselves by undergoing apoptosis.
The cytoskeleton is an intricate network of protein filaments that extend throughout the cytoplasm. It is responsible for large-scale movements, and without the cytoskeleton, wounds would never heal, muscles would be useless, and sperm would never reach the egg. The cytoskeleton is build on a framework of three types of protein filaments, and each type of filament has distinct mechanical properties and is formed from a different protein subunit.
Intermediate filaments: these are ropelike fibers made of intermediate filament proteins. One type of intermediate filaments forms a meshwork called the nuclear lamina just beneath the inner nuclear membrane. Other types extend across the cytoplasm, giving cells mechanical strength and distributing the mechanical stresses in an epithelial tissue by spanning the cytoplasm from one cell to another.
Microtubules: these are long, hollow cylinders made of the protein tubulin. They are more rigid than actin filaments or intermediate filaments. Microtubules have typically one end attached to a single microtubule-organizing center called a centrosome.
Actin filaments: these are flexible structures made of the protein actin. Although actin filaments are dispersed throughout the cell, they are most highly concentrated in the cortex (the layer of cytoplasm just beneath the plasma membrane)
The main function of intermediate filaments is to enable cells to withstand the mechanical stress that occurs when cells are stretched. Intermediate filaments are therefore present along the length of nerve cell axons, in muscle cells and in epithelial cells. In all these cells, intermediate filaments, by stretching and distributing the effect of locally applied forces, keep the cells and their membranes from breaking.
The filaments are called ‘intermediate’ because their diameter (10nm) is between that of the thin actin-containing filaments and the ticker myosin filaments of smooth muscle cells. Intermediate filaments are the toughest and most durable of the three types of cytoskeletal filaments. The intermediate filaments are found in the cytoplasm of most animal cells. They typically form a network throughout the cytoplasm, surrounding the nucleus and extending out to the cell periphery. Furthermore, intermediate filaments are also found within the nucleus as the nuclear lamina, which underlies and strengthens the nuclear envelope.
Intermediate filaments can be grouped intro four classes:
Keratin filaments in epithelial cells. Keratin filaments typically span the interiors of epithelial cells from one side to the cell to the other, and filaments in adjacent epithelial cells are indirectly connected through cell-cell junctions called desmosomes. This network distributes the stress that occurs when the skin is stretched. The importance of this function is illustrated by the rare genetic disease epidermolysis bullosa simplex, in which mutations in the keratin genes interfere with the formation of keratin filaments in the epidermis. As a result, the skin is highly vulnerable to mechanical injury, and even a gentle pressure can rupture its cell, causing the skin to blister.
Vimentin and vimentin-related filaments in connective-tissue, muscle and neuroglial cells
Neurofilaments in nerve cells
Nuclear lamins, which strengthen the nuclear membrane of all animal cells
Filaments of each class are formed by polymerization of their corresponding protein subunits. Plectin aids in the bundling of intermediate filaments and links these filaments to other cytoskeletal protein networks. Mutations in the gene for plectin cause a devastating disease that combines features of epidermolysis bullosa simplex, muscular dystrophy and neurodegeneration. Thus, although plectin may not be necessary for the initial formation of intermediate filaments, its cross-linking action is crucial to withstand the mechanical stress.
Microtubules are stiff, hollow tubes formed by polymerization of tubulin dimer subunits. They are polarized structures with a slow-growing ‘minus’ end (the a-tubulin end) and a fast-growing ‘plus’ end (the b-tubulin end). Microtubules are nucleated in, and grow out from, organizing centers such as the centrosome. The minus ends of the microtubules are embedded in the organizing center. Centrosomes contain hundreds of ring-shaped structured formed from another type of tubuline, g-tubulin, and each g-tubulin ring serves as the starting point (or nucleation site) for the growth of one microtubule.
Once a microtubule has been nucleated it has in a labile, dynamic state in which the microtubule alternate between a growing state and a shrinking state. These transitions, known as dynamic instability, are controlled by the hydrolysis of GTP bound to tubulin dimers. Each tubulin dimer has a tightly bound GTP molecule that is hydrolyzed to GDP after the tubulin assembles into a microtubule. GTP hydrolysis reduces the affinity of the subunit for its neighbors and decreases the stability of the polymer, causing it to dissemble. In this way, GTP hydrolysis controls the growth of microtubules.
The relative instability of microtubules allows them to undergo continual rapid remodeling, and this is crucial for microtubule function, as demonstrated by the effect of drugs that prevent polymerization or depolymerization of tubulin. If a cell in mitosis is exposed to the drug colchicine, which binds tightly to free tubulin and prevents its polymerization into microtubules, the mitotic spindle rapidly disappears and the cell is unable to partition its chromosomes into two groups. This shows that the mitotic spindle is normally maintained by a continuous balanced addition and loss of tubulin subunits. The inactivation or destruction of the mitotic spindle will eventually kill dividing cells.
Cells are able to modify the dynamic instability of their microtubules for particular purposes. When a cell has differentiated into a specialized cell type and taken on a definite fixed structure, the dynamic instability of its microtubules or along their length and stabilize them against disassembly. The stabilized microtubules then serve to maintain the organization of the cell. Proteins that capture the plus end can stabilize microtubules. Its important to realize that the microtubules in living cells do not act alone.
Intracellular transport is generated by motor proteins, which bind to actin filaments or microtubules and use the energy derived from repeated cycles of ATP hydrolysis to travel along the actin filament or microtubule in a single direction. Motor proteins move along microtubules using their globular heads and they belong to two families:
Kinesins and dyneins both have two globular ATP-binding heads and a tail. The globular heads are enzymes with ATP-hydrolyzing (ATPase) activity. This reaction provides the energy for a cycle of conformational changes in the head that enable it to move along the microtubule by a cycle of binding, release, and rebinding to the microtubule. Finally, microtubules and their associated motor proteins play an important part in positioning membrane-enclosed organelles within a eukaryotic cell.
As mentioned earlier in this summary, many microtubules in cells are stabilized through their association with other proteins, and therefore no longer show dynamic instability. This is seen in cilia and flagella that contain a bundle of stable microtubules. Bending of the microtubules, driven by a motor protein called ciliary dynein, causes their beating.
Actin filaments are found in all eukaryotic cells and are essential for many of their movements, especially those involving the cell surface. Like microtubules, many actin filaments are unstable, but they can also form stable structures in cells, such as the contractile apparatus of muscle. The varied forms and functions of actin filaments in cells depends on multiple actin-binding proteins. These control the polymerization of actin filaments, cross-link the filaments into loose networks or stiff bundles, attach them to membranes, or move them relative to one another.
Actin filaments are helical polymers of actin molecules. They are thinner, more flexible, and shorter than microtubules. Furthermore, actin molecules rarely occur in isolation in the cell; they are generally found in cross-linked bundles and networks, which are much stronger then the individual filaments.
Actine filaments are polarized structures with a fast- and a slow-growing end; the rate of growth is faster at the plus end than at the minus end. A ‘naked’ actin filament is unstable and can disassemble from both ends. Each free actin monomer carriers a tightly bound ATP, which is hydrolyzed to ADP soon after the incorporation of the actin monomer into the filament. Hydrolyses of ATP to ADP reduces the strength of binding between monomers and decreases the stability of the polymer. This hydrolysis thereby promotes depolymerization, helping the cell to disassemble filaments after they have formed. As for microtubules, the ability to assemble and disassemble is required for many of the functions performed by actin filaments.
Drugs like cytochalasins prevent actin polymerization, and others like jasplakinolides stabilize actin filaments against depolymerization. Addition of these toxins freezes cell movements.
Although actin is found throughout the cytoplasm of a eukaryotic cell, in most cells it is concentrated in the layer just beneath the plasma membrane, also known as the cell cortex. In this region actin filaments are linked by actin-binding proteins into a meshwork that supports the outer surface of the cell and gives it mechanical strength. In this way, actin filaments are responsible for the shape and movement of the cell surface, including the movements involved when a cell crawls along a surface. For this kind of movements are three interrelated processes required; all these three processes involve actin, but in different ways:
The cell pushes out protrusions at its front, or leading edge; this is driven by actin polymerization. The leading edge of a crawling cell regularly extends thin, sheetlike lamellipodia, which contain a dense meshwork of actin filaments. Many cells also extend thin, stiff protrusions called filopodia, which also contains a bundle of actin filaments. The formation and growth of actin filaments at the leading edge of a cell is assisted by various actin-binding accessory proteins, one set of proteins, the actin-related proteins or ARPs, promote the formation of branched actin filaments. These proteins form a complex that binds to the existing actin filaments, where they nucleate the growth of a new filament, which grows out at an angle to form a side branch. With the aid of additional actin-binding proteins, this web of actin undergoes assembly at the front end and disassembly at the back, pushing the lamellipodia to the front.
When the lamellipodia and filopodia touch down on a favorable patch of surface, the transmembrane proteins in their plasma membrane, known as integrins, adhere to molecules in the extracellular matrix on the surface of another cell over which the moving cell is crawling.
Meanwhile, on the intracellular face of the membrane of the crawling cell, integrins capture actin filaments, thereby creating an anchorage for the system of actin filaments inside the cell. The rest of the cell drags itself forward by traction on these anchorage points. This too depends on actin, but through the interaction of actin filaments with motor proteins known as myosins.
A variety of actin-binding proteins are thus required to drive the leading edge of a migrating cell forward, to adhere to the substratum, and to retract its trailing edge. All of these processes are triggered by external stimuli working via small GTP-binding proteins.
Myosins are motor proteins that use the energy of ATP hydrolysis to move along actin filaments: they can carry organelles along actin-filament tracks or cause adjacent actin filaments to slide past each other in contractile bundles. There are several different types of myosins in cells, of which the myosin-I and myosin-II subfamilies are most abundant. Myosin-I is found in all types of cells, and the myosin-I molecules have only one head domain and a tail. The head domain interacts with actin filaments and has ATP-hydrolyzing motor activity; the tail varies among the different types of myosin-I.
Muscle myosin belongs to the myosin-II subfamily of myosins, all of which have two ATPase heads and a long, rodlike tail. Each myosin-II molecule is a dimmer composed of a pair of identical myosin molecules held together by their tails; it has two ATPase heads at one end and e single coiled-coil tail at the other. Clustering of myosin-II molecules bind to each other through their coiled-coil tails, forming a bipolor myosin filament in which the heads project from the side.
In muscle, huge arrays of overlapping actin filaments and myosin filaments generate contractions by sliding over one another. One set of heads binds to acting filaments in one orientation and moves them in one way; the other set of heads binds to other actin filaments in the opposite orientation and moves them in the opposite direction.
The long fibers of skeletal muscle are huge single cells formed by the fusion of many separate smaller cells. A skeletal muscle cell is packed with myofibrils, which consists of a chain of identical tiny contractile units, or sacromeres. Sacromeres are highly organized assemblies of two types of filaments: actin filaments and filaments of muscle-specific myosin-II. Myosin filaments are centrally positioned in each sacromere, whereas the actin filaments extend inward from each end of the sacromere and overlap the ends of the myosin filaments.
The contraction of a muscle cell is caused by simultaneous shortening of all the sacromeres, which in turn is caused by the actin filaments sliding past the myosin filaments, with no change in the length of either type of filament. When a muscle is stimulated to contract, the myosin heads start to walk along the actin filament in repeated cycles of attachment and detachment. During each cycle, a myosin head binds and hydrolyzes one molecule of ATP. After a contraction is completed, the myosin heads lose contact with the actin filaments completely, and the muscle relaxes.
The molecular interaction between myosin and actin filaments takes place only when the skeletal muscle receives a signal from the nervous system. The signal from a nerve terminal triggers an action potential, which caused a release of Ca2+ in the cytosol. As mentioned earlier in this summary, Ca2+ is widely used as an intracellular signal to rely a message from the exterior to the internal machinery of the cell. In the case of muscle, the Ca2+ interacts with a molecular switch made of specialized accessory proteins. One of these proteins is tropomyosin, a molecule that binds in the groove of the actin helix and prevents the myosin heads from associating with the actin filament. The other is troponin, a complex that includes a Ca2+-sensitive protein (troponin-C), which is associated with the end of a tropomyosin molecule. When the level of Ca2+ rises in the cytosol, Ca2+ binds to troponin and induces a change in its shape. This in turn causes the tropomyosin molecules to shift their position, allowing myosin heads to bind to the actin filament and initiating contraction.
All living organisms are products of repeated rounds of cell growth and division extending back in time to the beginnings of life over three billion years ago. A cell reproduces by carrying out an orderly sequence of events in which it duplicates its contents and then divides in two. This cell cycle is the essential mechanism by which all living things reproduce. To ensure correct progression through the cell cycle, eukaryotic cells have evolved a complex network of regulatory proteins, known as the cell-cycle control system.
The most basic function of the cell cycle is to duplicate accurately the vast amount of DNA in the chromosomes and then precisely distribute the copies into genetically identical daughter cells. The duration of the cell cycle varies greatly from one cell type to another.
The eukaryotic cell cycle consists of four distinct phases. In the M phase two events occur: dividing of the nucleus, a process called mitosis and dividing of the cytoplasm, a process called cytokinesis. The period between one M phase and the next is called interphase, in which the cell increases in size and encompass the remaining three phases of the cell cycle. During S phase (S=synthesis), the cell replicates its nuclear DNA. S phase is flanked by two phases in which the cell continues to grow. The G1 phase (G=gap) is the interval between the completion of M phase and the beginning of the S phase. The G2 phase in the interval between the end of S phase and the beginning of M phase. During these gap phases, the cell monitors the internal and external environments to ensure that conditions are suitable and preparations are complete. At particular points in G1 and G2 the cell decides whether to proceed to the next phase or pause to allow more time to prepare.
The first visible sign that a cell is about to enter the M phase is the progressive condensation of its chromosomes, which were replicated earlier during S phase. Chromosome condensation thus marks the end of the G2 phase, and at this stage in the cell cycle the replicated chromosomes become visible in the light microscope.
The essential processes of the cell cycle, such as DNA replication, mitosis, and cytokinesis, are triggered by a cell-cycle control system. The events of the cell cycle must occur in a particular sequence, and this sequence must be preserved even if one of the steps takes longer than usual. The cell-cycle control system achieves all of this by means of molecular brakes that can stop the cycle at various checkpoints. Two important checkpoints occur in G1 and G2:
The G1 checkpoint allows the cell to confirm that the environment is favorable for cell proliferation and its DNA is intact before committing to S phase. Cell proliferation depends of nutrients and specific signal molecules in the extracellular environment. If extracellular conditions are unfavorable cells can delay progress through G1 and may even enter a specialized resting state known as G0.
The G2 checkpoint ensures that cells do not enter mitosis until damaged DNA is repaired and DNA replication is completed.
The cell-cycle control system coordinates the events of the cell cycle by cyclically switching on the appropriate parts of the cell-cycle machinery and then switching them off. As discussed earlier in this summary, phosphorylation followed by dephosphorylation is one of the most common ways used by cells to switch the activity of a protein on and then off, and the cell-cycle control system uses this mechanism repeatedly. The phosphorylation reactions are carried out by a specific set of protein kinases, enzymes that transfer a phosphate group from ATP to a particular amino acid side chain of the target protein. Switching these protein kinases on and off at the appropriate times is regulated by a second set of protein components of the control system: cyclin-dependent protein kinases (Cdks).
Different cyclin-Cdk complexes trigger different steps of the cell cycle:
Synthesis of M-cyclin starts immediately after cell division. Activated M-Cdk indirectly activates more M-Cdk; this explosive increase in M-Cdk activity drives the cell abruptly into M phase. Its rapid elimination then helps initiate the exit from mitosis. This elimination is the result of the ubiquitin-dependent proteolytic system. As mitosis nears completion, multiple molecules of the protein ubiquitin are attached to the M-cyclin molecules. This ubiquitination marks the cyclin for degradation in proteasomes, large proteolytic machines found in all eukaryotic cells. A protein complex called the anaphase promoting complex (APC) adds ubiquitin to the cyclin and to other proteins involved in the regulation of mitosis. Destruction of the cyclin inactivates the Cdk.
As we discussed earlier, DNA replication begins at origins of replication. These sequences recruit specific proteins that control the initiation and completion of DNA replication. One multiprotein complex, the origin recognition complex (ORC), remains bound to the origins of replication throughout the cell cycle, where it serves as a sort landing pad for additional regulatory proteins that bind before the start of S phase. One of these regulatory proteins is called Cdc6, which concentration increases in early G1. When Cdc6 binds to ORCs in G1, it promotes the binding of additional proteins to form a pre-replicative complex. S-Cdk then triggers origin firing by causing the assembly of DNA polymerase and the initiation of DNA synthesis. S-Cdk also helps block replication by helping to phosphorylate Cdc6, which dissociated from the origin and is degraded.
The cell-cycle can be halted by at least two mechanisms:
1Cdk inhibitor proteins can block the assembly or activity of one or more cyclin-Cdk complexes. This is seen when checkpoints mechanisms halts the cell cycle in G1 if DNA is damaged, helping to ensure that a cell does not replicated damaged DNA. When DNA is damaged, the p53 protein, which is normally rapidly degraded, is stabilized and activated. This is partly because p53 becomes phosphorylated by specific protein kinases that are activated in response to DNA damage. Activated p53 accumulates and stimulates the transcription of the gene that encodes the Cdk inhibitor protein p21. The p21 protein binds to G1/S-Cdk and S-Cdk and inactivates them, so that the cell cycle arrests in G1. If p53 is missing of defective, the replication of damaged DNA leads to a high rate of mutations and the production of cells that tend to become cancerous. In fact, mutations in the p53 gene are found in about half of all human cancers.
Components of the control system can stop being made, for example when cells enter G0. It seems to be a general rule that cells will multiply only if they are stimulated to do so by signals from other cells. If deprived of such signals, the cell cycle arrests at a G1 checkpoint and enters the G0 state.
Animal cell numbers are not only regulated by controlling the rate of cell division, but also by controlling the rate of cell death. If cells are no longer needed, they commit suicide by activating an intracellular death program. This process is therefore called programmed cell death, although it is more commonly called apoptosis. In adult tissues, cell death exactly balances cell division. If this were not so, the tissue would grow or shrink.
Cells that die as a result of acute injury typically swell and burst, spilling their contents all over their neighbors, a process called cell necrosis. By contrast, a cell that undergoes apoptosis dies neatly, without damaging its neighbors. A cell in apoptosis shrinks and condenses. The cytoskeleton collapses, the nuclear envelope disassembles, and the nuclear DNA breaks up into fragments. Most important, the cell surface is altered in such a manner that it immediately attracts phagocytic cells, usually specialized phagocytic cells called macrophages. These cells engulf the apoptotic cell before it spills its contents. This rapid removal of the dying cell avoids the damaging consequences of cell necrosis, and also allows the organic components of the apoptotic cell to be recycled by the cell that ingests it.
Apoptosis is carried out by a family of proteases called caspases. The caspases are made as inactive precursors called procaspases, which are themselves activated by proteolytic cleavage in response to signals that induce apoptosis. The activated caspases cleave, and thereby activate, other members of the family, resulting in an amplifying proteolytic cascade.
The main proteins that regulate the activation of procaspases are members of the Bcl-2 family of intracellular proteins. Some members of this protein family promote procaspase activation and cell death, whereas others inhibit these processes. Two of the most important death-promoting family members are proteins called Bax and Bak. These proteins activate procaspases indirectly, by inducing the release of cytochrome c from mitochondria into the cytosol. Cytochrome c binds to an adaptor protein, which then activates a specific procaspase. This activated procaspases initiates the caspase cascade that leads to apoptosis.
Most of the extracellular signal molecules that influence cell division, cell growth, and cell survival are soluble proteins secreted by other cells or proteins bound to the surface of other cells or the extracellular matrix. Although most act positively to stimulate one or more of these cell processes, some act negatively to inhibit a particular process. The positively acting signal proteins can be divided into three major classes based on their function:
Mitogens: animal cells proliferate only if stimulated by mitogens, which activate intracellular signaling pathways to override the normal brakes that otherwise block cell-cycle progression; this mechanism ensures that a cell divides only when another cell is needed.
Growth factors: for an organism or an organ to grow, cells must grow as well as divide. Animal cell growth depends on extracellular growth factors, which stimulate protein synthesis and inhibit protein degradation.
Survival factors: most animal cells require continuous signaling from other cells to avoid apoptosis; and this may be a mechanism to ensure that cells survive only when and where they are needed.
Cancer cells fail to obey these normal ‘social’ controls on cell behavior and therefore outgrow, out-divide and out-survive their normal neighbors.
We take a closer look to the final phase of the cell cycle, when the cell divides its nucleus (mitosis) and then its cytoplasm (cytokinesis). Together, mitosis and cytokinesis constitute M phase of the cell cycle.
When the chromosomes are duplicated in S phase, the two copies of each duplicated chromosome (called sister chromatids) remain tightly bound together by cohesins. A set of protein complexes, called condensins, helps to carry out chromosome condensation when the cell is about to enter the M phase. Together, cohesins and condensins help reduce the mitotic chromosomes to small, condensed structures that can be easily segregated during mitosis. M phase is initiated by the phosphorylation triggered by activated M-Cdk.
To produce two identical daughter cells, a mitotic spindle is formed during M phase. This mitotic spindle is composed of microtubules and the various proteins that interact with them, including microtubule-associated motor proteins. In animal cells and many unicellular eucaryotes, a different cytoskeletal structure is responsible for cytokinesis. It is called the contractile ring because it consists mainly of actin filaments and myosin filaments arranged in a ring around the equator of the cell. As the ring contracts, it pulls the membrane inward, thereby dividing the cell in two. The microtubules bind to protein complexes called kinetochores, associated with the centromere of each sister chromatid.
However, before M phase begins two critical events must be completed: DNA must be fully replicated and the centrosome must be duplicated. Each centrosome consists of proteins that contain hundreds of g-tubulin rings. These ring complexes serve as nucleation sites for the growth of microtubules that radiate out from the centrosome. During interphase of each cell cycle, the centrosome is duplicated and as mitosis begins the two centrosomes separate, each of which nucleates its own aster. The two asters move to opposite sides of the nucleus to form the two poles of the mitotic spindle. When the nuclear envelope breaks down, the spindle microtubules invade the nuclear area and capture the replicated chromosomes. The process of centrosome duplication and separation is known as the centrosome cycle.
Although M phase proceeds as a continuous sequence of events, it is traditionally divided into six stages. The first five stages of M phase constitute mitosis, and cytokinesis occurs in the sixth stage, which overlaps with the end of mitosis.
The six stages are:
Prophase: at the beginning of the prophase, the two daughter centrosomes separate. They now organize their own array of microtubules and being to move to opposite poles of the cell, driven by centrosome-associated motor proteins that use the energy of ATP hydrolysis to move along the microtubules. During prophase, some of the microtubules growing from one centrosome interact with the microtubules from the other centrosome; this interaction stabilizes the microtubules.
Prometaphase: this starts abruptly with the disassembly of the nuclear envelope, which breaks up into small membrane vesicles. This process is triggered by the phosphorylation and consequent disassembly of the intermediate filament proteins of the nuclear lamina. Chromosomes can now attach to spindle microtubules via their kinetochores and undergo active movements.
Metaphase: the chromosomes are aligned at the equator of the spindle, midway between the spindle poles. The paired kinetochore microtubules on each chromosome attach to opposite poles of the spindle.
Anaphase: this begins abruptly with the release of the cohesin linkage that holds the sister chromatids together. This allows each chromatid (now called a daughter chromosome) to be gradually pulled to the spindle pole to which it is attached. This movement segregates the two identical sets of chromosomes to opposite ends of the spindle. The abrupt disruption of the cohesin linkage is triggered by the activation of the anaphase-promoting complex (APC). Once this proteolytic complex is activated, it cleaves an inhibitory protein, thereby releasing a proteolytic enzyme that breaks the cohesin linkage. The anaphase is separated in two processes: in anaphase A the kinetochore microtubules shorten by depolymerization, and the attached chromosomes move poleward. In anaphase B, the spindle poles themselves move apart, further contributing to the segregation of the two sets of daughter chromosomes.
Telophase: the two sets of daughter chromosomes arrive at the poles of the spindle. A new nuclear envelope reassembles around each set, completing the formation of two nuclei and marking the end of mitosis. The division of the cytoplasm begins with the assembly of the contractile ring.
Cytokinesis: in animal cells, cytoplasmatic division is mediated by a contractile ring of actin filaments and myosin filaments, which assembles midway between the spindle poles and contracts to divide the cytoplasm in two; in plant cells, by contrast, cell division occurs by the formation of a new cell wall inside the cell, which divides the cytoplasm in two.
Together, the six stages form a dynamic sequence in which many independent cycles are coordinated to produce two genetically identical daughter cells.
The process of mitosis ensures that each daughter cell receives a full complement of chromosomes. But when a eucaryotic cell divides, each daughter cell must also inherit all of the other essential cell components, including the membrane-enclosed organelles. Therefore, large membrane-enclosed organelles such as the endoplasmatic reticulum and Golgi apparatus break into many smaller fragments during M phase. Other components of the cell, including all of the soluble proteins, are inherited randomly when the cell divides its cytoplasm in the final stage of the M phase.
Most of the organisms around us reproduce sexually. However, reproduction without sex is possible; bacteria and other single-celled organisms can reproduce by simple cell division. While asexual reproduction is simple en direct, it usually gives rise to offspring that are genetically identical to the parent organisms. Sexual reproduction, on the other hand, involves the mixing of genomes from two individuals to produce offspring that are genetically distinct from one another and from both their parents. This way of reproduction has great advantages. One advantage seems to be that the reshuffling of the genes through sexual reproduction can help a species survive in an unpredictably variable environment. If two parents produce many offspring with a wide variety of gene combinations, the chance that at least one of their progeny will have the combinations of features necessary for survival is increased.
Sexual reproduction occurs in diploid organisms, in which each cell contains two sets of chromosomes, one inherited from each parent. The specialized cells that carry out sexual reproduction (the germ cells, or gametes) are haploid: they each contain only one set of chromosomes. These haploid germ cells are generated when a diploid cell undergoes the process of cell division called meiosis. During meiosis the chromosomes of the double chromosome set are portioned out into single chromosome sets. The two different haploid gametes then fuse to make a diploid cell (the zygote) with a new combination of chromosomes. The zyg ote thus produces develops into a new individual with a diploid set of chromosomes, which differs from that of either parent. In this way, a distinction can be drawn between the cells of the germ line (from which the next generation of gametes will be derived) and the somatic cells (which form the rest of the body).
Sexual reproduction thus involves the cyclic alternation of diploid and haploid states: diploid cells divide by meiosis to form haploid gametes, and the haploid gametes from two individuals fuse as fertilization to form a new diploid cell.
During meiosis, the maternal and paternal chromosomes of a diploid cell are parceled out to gametes so that each gamete receives one copy of each chromosome. Because the assortment of the two members of each chromosome pair occurs at random, many genetically different gametes can be produced from a single individual.
Before a cell divides – by either meiosis or mitosis – it first duplicates all of its chromosomes. The twin copies of each fully replicated chromosome at first remain tightly linked along their length and are called sister chromatids. However, the way these replicated chromosomes are handled differs in meiosis and mitosis. In mitosis the replicated chromosomes line up at random order at the metaphase plate; as mitosis continues, the two previously joined sister chromatids then separate from each other to become individual chromosomes. The events that occur in the first meiotic cell division mirror the sequence of stages that a cell goes through in mitosis: in prophase, the replicated chromosomes condense; in metaphase, they align at the equator of the meiotic spindle; and in anaphase, they are segregated to the poles. In this first meiotic division the homologous maternal and paternal chromosomes have paired before lining up at the metaphase plate.
After the duplicated homologs pair, genetic recombination is initiated, also called crossing-over. Crossing-over ensures the proper segregation of homologous chromosomes and enhances the genetic reassortment that occurs during meiosis by exchanging genes between them. The structure formed when homologous chromosomes pair is called a bivalent and consists of four chromatids. Cross-over events between a maternal and paternal chromatid in paired chromosomes forms a chiasma (a connection that corresponds to a crossover between two non-sister chromatids). The combination of the chiasmata and the tight attachment of the sister chromatids to each other mediated by cohesin proteins, holds the two duplicated homologs together until the spindle separates then at anaphase I. In most organisms, recombination during meiosis is required for the correct segregation of the two duplicated homologs into separate daughter nuclei.
The first meiotic division does not produce cells with a haploid amount of DNA. To achieve this goal, each cell proceeds through a second round of division, meiosis II, which occurs without further DNA replication and without any significant interphase period. A spindle forms, the chromosomes align at its equator, and the sister chromatids separate to produce daughter cells with a haploid DNA content. In meiosis II, as in mitosis, the kinetochores on each sister chromatid function independently and the cohesins holding the sister chromatids together at the centromere are degraded, allowing the two sister chromatids to be pulled to opposite poles.
Although most of the mechanical features of meiosis are similar to those of mitosis, the behavior of the chromosomes is different: meiosis produces four genetically dissimilar haploid cells by two consecutive cell divisions, whereas mitosis produces two genetically identical diploid cells by a single cell division. Whereas mitosis and division II of meiosis usually occur within hours, division I of meiosis can last days, month, or even years, due to the long time spent in prophase.
Occasionally, homologs fail to separate properly, a phenomenon known as nondisjunction. As a result, some of the haploid cells that are produced lack a particular chromosome, while others have more then one copy of it. Upon fertilization, such gametes form abnormal embryos, most of which die. However, some survive: Down syndrome, caused by an extra copy of Chromosome 21, is a human disease characterized by severe mental retardation. This extra copy results from nondisjunction of a Chromosome 21 pair during meiosis, giving rise to a gamete that contains two copies of Chromosome 21 instead of one copy. When this abnormal gamete fuses with a normal gamete at fertilization, the resulting embryo contains three copies of Chromosome 21 instead of two.
Regardless of whether the segregation error occurs in the sperm or the egg, nondisjunction is thought to be one of the reasons for the high rate of miscarriages (spontaneous abortion) in early pregnancy in humans.
Mendel unraveled the laws of heredity by studying the inheritance of a handful of discrete traits in garden peas. He supposed that for any pair of alleles, one allele is dominant and the other is recessive. The ideas of homozygosity and heterozygosity are also his. One important consequence of heterozygosity, and of dominance and recessiveness, is that not all of the alleles an individual carries can be detected in its phenotype. Humans have about 30.000 genes, and each of us is heterozygous for a very large number of these. Thus, we all carry a great deal of genetic information that remains hidden in our personal phenotype, but that can turn up in future generations.
The law of segregation states that the maternal and paternal alleles for each trait separate from one another during gamete formation, then reunite at random during fertilization. This law permits us to predict the phenotypes that will result from a particular cross-breeding experiment. Mendel’s law of segregation also explains the 3:1 ratio that can be observed in the F2 generation of heterozygous inheritance. But his rules governing inheritance are not limited to reproduction in plants. Mendel’s concept of the gene and his law of segregation can be generalized to all sexually reproducing organisms, including humans.
The law of independent assortment states that during gamete formation, different alleles segregate independently of each other. Furthermore, the behavior of chromosomes during meiosis explains Mendel’s laws. During meiosis, each set of paired homologs attaches to the spindle independently. This random arrangement of chromosomes on the metaphase spindle is reflected in Mendel’s law of independent assortment, since gene on different chromosomes will be inherited independently.
Mendel’s observation that different genes assort independently does not necessarily require that the genes lie on different chromosomes. Genes that are far enough away from one another on the same chromosome will also sort independently due to the recombination that occurs during prophase of meiosis I. In this way, if genes lie close together on a chromosome they tend to be inherited as a unit. By measuring how frequently genes are co-inherited, researchers can determine whether genes reside on the same chromosome and, if so, how far apart they lie. This type of information has been used to map the relative positions of the genes on each chromosome of many organisms. Such genetic maps have been crucial for cloning of human disease genes such as the gene for cystic fibrosis.
Mutant alleles can be either dominant or recessive. If the heterozygous organism has a mutant phenotype, the mutant allel is dominant; if it has a normal phenotype, the mutant allel is recessive. So, the key to determining whether a particular allele is dominant or recessive lies in the phenotype of the heterozygote.
Mutations have very different consequences, some confer a selective advantage, whether others cause defects and make the organisms less likely to survive. However, even deleterious mutations can benefit an organism, as individual genes can have multiple effects on phenotype. Take sickle-cell anemia in humans: this disorder is caused by a mutation in the gene encoding for b-globin, one of the polypeptides that make up hemoglobin. The sickle-cell mutation directs the formation of an abnormal polypeptide that causes red blood cells to adopt to a sickled shape. These misshapen cells clog small blood vessels, reducing the amount of oxygen that can reach different tissues, causing a variety of symptoms including muscle cramps and even heart failure. But the sickle-trait also has its benefits! Individuals who are heterozygous or homozygous for the sickle-mutation, are resistant to malaria. This is because the organism that causes the disease is unable to reproduce in sickle-shaped red blood cells, which fragment before the parasite has a chance to multiply.
Before the advent of recombinant DNA technology, most genes were identified by observing he processes disrupted when the gene was mutated. Although spontaneous mutations can sometimes be found by examining extremely large populations the process of identifying interesting mutants can be made much more efficient by generating mutations with agents that damage DNA, called mutagens. Different mutagens can generate different types of DNA alterations. And such mutants can then be screened to identify phenotypes of interest and, ultimately, to isolate the responsible genes.
Unlike worm and flies, humans are not suitable for experiments with mutagens, because they do not reproduce rapidly and any human with a serious defect in an essential process, such as DNA replication, would die long before birth. We study human genes, by studying less complex organisms which genes can reveal critical information about similar genes and processes in humans. And secondly, by analyses of the phenotypes of individuals with spontaneous mutations (like sickle-cell anemia), together with studies of their cultured cells, have provided many unique insights into important human gene function.
A large-scale genetic screen can turn up many different mutants that have the same phenotype. These defects might lie in different genes that function in the same process, or they might represent different mutations in the same gene. Complementation tests can be used to ascertain whether the mutations fall in the same or in different genes. In the simplest type of complementation test, an individual that is homozygous for one mutation is mated with an individual that is homozygous for the other mutation. If the two mutations are in the same gene, the offspring will show the mutant phenotype, because they carry only defective copies of the gene in question. If, in contrast, the mutations fall in different genes, the resulting offspring will show ‘the normal phenotype’ because they will have one normal copy (and one mutant copy) of each gene. The mutations thereby complement one another and restore a normal phenotype.
With the exception of identical twins, no two humans genomes are alike. Each of us carries a unique set of polymorphisms – changes in nucleotide sequence – that shapes our individual phenotypes. Single-nucleotide polymorphisms (SNPs) are DNA sequences that differ by a single nucleotide base between one portion of the population and another. They provide useful markers for performing genetic analyses that link a specific trait with a particular region of DNA. These polymorphisms can be used as markers for building genetic maps or for performing the genetic analyses that allow us to link particular polymorphisms with specific disease or predispositions to disease.
The problem is that any two humans differ about 0.1% in their nucleotide sequences. Theoretically, one would need to search through all 3 million of those polymorphisms to identify the one or two changes that are responsible for the differences. However, to reduce the number of polymorphisms one needs to examine, researchers are taking advantage of the recent discovery that human genes tend to be inherited in blocks. These haplotype blocks contain sets of alleles and SNPs that have been inherited as a group with little genetic rearrangement. The presence of such genetic clusters makes it easier to identify genes and mutations that are associated with human disease.
Many human traits run in families, have a genetically inherited component, but do not adhere strictly to Mendel’s laws. These complex traits are often polygenic; they arise from the interactions of multiple genes, each of which makes a small contribution to the phenotype. Although many human traits have a strong genetic basis, some are determined primarily by the environment. It is the interactions of our genetic makeup with our environment that make each of us unique.
Cells are the building blocks of multicellular organisms. Most of the cells are organized into cooperative assemblies called tissues. However, tissues are composed not only of cells, with their internal framework of cytoskeletal filaments and extracellular matrix. It is this matrix that gives supportive tissues their strength.
Plants and animals have evolved their multicellular organization independently, and their tissues are constructed on different principles. Because the cytoskeleton of plants lacks the tension-bearing intermediate filaments found in animal cells, and it has virtually no tensile strength. An external cell wall, therefore, is essential. Animal tissues are more diverse. Like plants, they consists of extracellular matrix as well as cells, but these components are organized in many different ways, including bone, muscle, and epidermis.
In plants, each cell surrounds itself with extracellular matrix in the form of a cell wall. Most newly formed cells in a multicellular plant initially make relatively then primary cell walls that are capable of slowly expanding to accommodate subsequent cell growth. The driving force for growth is a swelling pressure, called the turgor pressure, which develops due to an osmotic imbalance between the interior of the cell and its surroundings. Once growth stops and the wall no longer need to expand, a more rigid secondary cell wall is produced. Cellulose fibers give the plant cell wall its tensile strength. In woody tissue, a highly cross-linked lignin network is deposited within this matrix to make it more rigid and waterproof.
Because the cellulose fibers resist stretching, their orientation governs the direction in which the growing cell enlarges, or grows. Cellulose is synthesized on the outer surface of the cell by enzyme complexes embedded in the plasma membrane. These transport sugar monomers across the membrane and incorporate them into a set of growing polymer chains at their points of membrane attachment. Each set of chains forms a cellulose microfibril. The enzyme complexes move in the membrane, spinning out new polymers and laying down a trail of oriented cellulose fibers behind them. Just underneath the plasma membrane, microtubules are aligned exactly with the cellulose fiber outside the cell. These microtubules are thought to serve as tracks to guides the movement of the enzyme complexes. In this way, the orientation of the cytoskeleton controls shaping of the plant cell and the modeling of the plant tissue.
Cellulose fibers in the plant cell wall confer tensile strength; other cell wall components give resistance to compression.
There are four major types of tissues in animals: connective, epithelial, nervous, and muscular. But the basic distinction is between connective tissue and the rest. Animal connective tissues provide mechanical support and consist of extracellular matrix with sparsely scattered cells. In the extracellular matrix of animals, the tensile strength is provided not by a polysaccharide, as in plants, but by a fibrous protein called collagen. The various types of connective tissue owe their specific characters to the type of collagen that they contain, to its quantity, and to the other molecules that are interwoven it in varying proportions. The protein and polysaccharide components of the matrix are made by connective tissue cells embedded in it; in most connective tissues these cells are called fibroblasts; in bone they are called osteoblasts.
Some people have a genetic defect in the collagenase, so that their collagen fibrils do not assemble correctly. As a result, the skin and various other connective tissues have reduced tensile strength and are extraordinarily stretchable.
Cells must be able to attach to the matrix, but cells do not attach well to bare collagen. Another extracellular matrix protein, fibronectin, provides a linkage; one part of the fibronectin molecule binds to collagen, while another par forms an attachment site for a cell. The cell binds to the specific site by means of a receptor protein, called an integrin. While the extracellular domain of the integrin binds to fibronectine, the intracellular domain binds to actin filaments.
While collagen provides tensile strength to resist stretching; glycosaminoglycans (GAGs), covalenty linked to proteins to form proteoglycans, act as space-filters and provide resistance to compression.
Cells joined together in epithelial sheets line all external and internal surfaces of the animal body. An epithelial sheet has two faces: the apical surface is free and exposed to the air or to a watery fluid; the basal surface rests on some other tissue to which it is attached. Supporting the basal surface of the epithelium there lies a thin tough sheet of extracellular matrix, called the basal lamina, composed of a specialized type of collagen and various other molecules, including a protein called laminin. Laminin provides adhesive site for integrin molecules in the plasma membrane of the epithelial cells. The apical and basal faces of an epithelium are chemically different, reflecting a polarized internal organization of the individual epithelial cells.
In epithelial sheets, in contrast to connective tissue, tension is transmitted directly from cell to cell via cell-cell junctions. Several types of cell-cell junctions are found in epithelia in animals:
Tight junctions seal neighboring cells together in an epithelial sheet to prevent leakage of molecules between them. The tight junctions are formed from proteins called claudins and occludins, which are arranged in strands along the lines of junction to create the seal. As we saw earlier in this summary, tight junctions also play a key part in maintaining the polarity of the individual epithelial cells.
The junctions that hold an epithelium together by forming mechanical attachments are of three main types. Adherens junctions and desmosome junctions bind one epithelial cell to another, while hemidesmosomes bind epithelial cells to the basal lamina. Adherens junctions and desmosome junctions are both build around transmembrane proteins belonging to the same family, called cadherins. A cadherin molecule in the plasma membrane of one cell binds directly to an identical cadherin molecule in the plasma membrane of its neighbor, this kind of binding is called homophilic.
Proteins of the cadherin family span the epithelial cell membrane and bind to similar cadherins in the adjacent epithelial cell. At an adherens junction, the cadherins are linked intercellularly to actin filaments; at a desmosome junction, they are linked to keratin filaments. Actin bundles connected from cell to cell across an epithelium can contract, causing the epithelium to bend.
Gap junctions form channels that allow passage of small molecules and ions from cell to cell. Curiously, plant tissues, though they lack all the other types of cell-cell junctions, have a functional counterpart of the gap junction. The cytoplasms of adjacent plant cells are connected via minute communicating chancels called plasmodesmata, which span the intervening cell walls.
Although the final structure of an animal’s body may be enormously complex, it is generated by a limited repertoire of cell activities. Examples of all these activities have been discussed earlier in this summary. Trough cell division, cell growth, cell movement, and cell specialization, a fertilized egg cell gives rise to a multicellular animal. Almost every tissue in animals consists of a complex mixture of cell types that are subject to continual turnover. But throughout cell replacement and tissue renewal, the organization of the tissue must be preserved. Three key factors maintain the cellular organization of tissues:
Cell communication: to survive most cells have to receive signals from their environment. These communications ensure that new cells are produced and survive only when and where they are required
Selective cell-cell adhesion: because different cell types have different cadherins and other adhesion molecules in their plasma membranes, they tend to stick selectively (by homophilic binding) to other cells of the same type. Sometimes they form selective attachment to certain other cell types or to specific extracellular matrix components. The selectivity of adhesion prevents the different cell types in a tissue from becoming chaotically mixed
Cell memory: specialized patterns of gene expression, evoked by signals that acted during embryonic development, are maintained so that cells preserve their distinctive character and pass it on to their progency
Cells in tissue vary enormously in their rate and pattern of turnover. At one extreme are nerve cells, most of which last a lifetime without replacement. At the other extreme are the cells that line the intestine, which are replaced every few days. Between these extreme there is of course a spectrum of different rates and styles of cell replacement and tissue renewal. Our life depends on these renewal processes. A large dose of ionizing radiation, by blocking cell division, halts renewal.
Many of the differentiated cells that need continual replacement are themselves unable to divide. Red blood cells, surface epidermal cells, and the absorptive and goblet cells of the gut lining are all of this type; also referred as terminally differentiated cells. Replacement for terminally differentiated cells are generated from a stock of proliferating precursor cells, which themselves usually derive from small numbers of more slowly dividing stem cells. The stem cells and proliferating precursors cells are retained in the corresponding tissues along with the differentiated cells. When a stem cell divides, each daughter can either remain a stem cell or go on to become terminally differentiated. The pattern of replacement varies from one stem-cell-based tissue to another. Often, a single type of stem cell gives rise to several types of differentiated progency; the process of blood-cell formation, or hemopoiesis, provides an extreme example of the phenomenon. All of the different cell types in the blood ultimately derive from the same hemopoietic stem cell that normally inhabits the bone marrow.
Embryonic stem cells (ES cells) can be maintained indefinitely in culture and remain capable of differentiating into any cell type in the body. Perhaps one day it may even become possible to grow entire organs from ES cells by recapitulation of embryonic development. There is, however, one major problem associated with the use of ES cells for tissue repair. If the transplanted cells are genetically different from the cells of the patient into whom they are grafted, they are likely to be rejected and destroyed by the immune system.
By nuclear transplantation, personalized ES cells can in principle be produced for any adult, a technique called ‘therapeutic cloning’. In therapeutic cloning only cells are produced; in reproductive cloning a whole new multicellular individual is generated.
Foremost among the diseases of tissue renewal is cancer. In Europe and North America, one in four of us will die of cancer. Cancer cells fail to obey the social constraints that normally maintain tissue organization: they proliferate when they should not, survive where they should not, and invade regions that they should keep out of. It is the combination of these features that creates the lethal danger.
Epidemiology has provided strong evidence that the environment plays a part in the causation of most cases of cancer. Although it is still hard to discover which specific factors in the environment or life-style are critical, and many remain unknown, some of them have been identified quite precisely. Obesity, for example, is correlated with an increased cancer risk, and the relationship is suspected to be causal. By far the most important environmental cause of cancer, however, is tobacco-smoking, which is not only responsible for almost all cases of lung cancer, but also raises the incidence of several other cancers, such as those of the bladder.
Cancer is fundamentally a genetic disease: it arises as a consequence of pathological changes in the information carried by DNA. It differs from other genetic diseases in that the mutations underlying cancer are mainly somatic mutations as opposed to germ-line mutations. Most of the identified agents known to contribute to the causation of cancer are mutagens: they cause changes in the nucleotide sequence of DNA. But mutations can also occur spontaneously as a result of fundamental limitations on the accuracy of DNA replication and DNA repair. Nevertheless, it takes more than a single mutation to turn a normal cell into a cancer cell. In fact, cancer cells arise from the accumulation of many mutations in a single somatic cell lineage. And cancer, therefore, is typically a disease of old age.
To be successful, a cancer cell must acquire a whole range of abnormal properties as it evolves. Different cancers require different combinations of properties. Even though, there is a general list of key behaviors of cancer cells that distinguish them from normal cells:
Many diverse types of genes are critical for cancer. In some case, the dangerous mutations are ones that make the affected gene product hyperactive. These mutations have a dominant effect and the mutant gene is called an oncogene; the corresponding normal form of the gene is then called a proto-oncogene. For other genes, the danger lies in mutations that destroy gene function. These mutations are generally recessive and the affected gene is called a tumor suppressor gene. Tumor suppressor genes can sometimes be identified through studies of rare cancer-prone families in which a mutation of one gene copy is inherited.
Colorectal cancer illustrates how loss of a gene can lead to growth of a tumor. Colorectal cancer arises from the epithelium lining the colon and rectum; most cases are seen in old people and do not have any discernible hereditary cause. A small proportion of cases, however, occur in families that are exceptionally prone to the disease and show an early onset. In one set of families, the predisposition to cancer has been traced to an inherited mutation in a DNA repair enzyme. In another class of hereditary colorectal cancer patients, a different mutation is present, leading to a highly distinctive phenotype. The affected individuals develop colorectal cancer in early adult life, and the onset of their disease is foreshadowed by the development of hundreds of thousands of little tumorous growths, called polyps, in the lining of the colon and rectum. The abnormality can be traced to deletion or inactivation of a gene called the adenomatous polyposis coli (APC) gene. Affected individuals inherit one mutant copy of the gene and one normal copy; their cancers arise from cells that can be shown to have undergone a somatic mutation that inactivates the remaining good copy. All this identifies APC as a tumor suppressor gene. When APC is lost, the ‘Wnt pathway’ (which is involved in stimulating cell proliferation in crypts of the gut lining) is hyperactive and the cells proliferate to excess, generating a polyp. Within this growing mass of tissue, further mutations may occur, resulting in invasive cancer.
An understanding of cancer cell biology opens the way to new treatments. At this moment, surgery remains the most effective tactic in many cancer, and surgical techniques are continually improving. Where surgery fails, therapies based on the intrinsic peculiarities of cancer cells can be used. One promising strategy for the future is to block formation of the new blood vessels that normally invade a growing tumor, and so to choke tumor growth by depriving the cells of their blood supply. Another strategy aims to use antibodies that bind to the tumor-specific cell surface proteins; the antibodies can be coupled to toxins or toxin-generating enzymes that will kill the targeted cancer cells.
With our modern understanding of the molecular biology of cancer, we hoop it will be possible to dives effective methods of treatment for a still wider range of forms of cancer.
Notes bij Gezonde en Zieke Cellen 1 (2015-2016)Deze aantekeningen zijn gebaseerd op 2015-2016
De cel is de kleinste organische eenheid in het lichaam en wordt afgesloten door een membraan. In de cel zitten verschillende organellen met een eigen functie, die ook omhuld worden door een membraan. De verschillende organellen die zich in de cel bevinden zijn de celkern, het golgi apparaat, het peroxisoom, het lysosoom, de mitochondria, vesicels en het endoplasmatisch reticulum. Door middel van aankleuren kunnen onder de microscoop de verschillende onderdelen van de cel en de aanwezige eiwitten duidelijker zichtbaar worden gemaakt. Cellen zijn heel dynamisch door de eiwitten in de cel. Er zijn verschillende soorten cellen met verschillende vormen en maten. Een spiercel ziet er anders uit dan een epitheelcel. Ook hebben fibroblasten bijvoorbeeld een hele andere functie dan spiercellen. Fibroblasten zijn cellen van het bindweefsel die collageen produceren en dus stevigheid geven aan weefsels, terwijl spiercellen voor beweging zorgen. Cellen vermenigvuldigen, sterven en specialiseren zich en daarnaast werken ze samen met en communiceren ze met andere cellen. De cel bestaat voor een groot gedeelte uit water en is een goed oplosmiddel voor polaire stoffen. De mens bestaat voor 70% uit water. Hydrofiele stoffen zijn stoffen die goed oplosbaar zijn in water en hydrofobe stoffen lossen niet op in water. Water is belangrijk, omdat het een oplosmiddel is voor hydrofiele (polaire) stoffen. Water is zelf ook een polair molecuul, wat betekent dat de negatieve en positieve lading in het molecuul niet gelijk verdeeld zijn. Water verdrijft polaire (hydrofobe) stoffen, zoals bijvoorbeeld vet. De cel maakt gebruik van amfipathische/amfifiele stoffen, die aan de ene kant een polaire kop en aan de andere kant een apolair (hydrofobe) staart (vetzuur) hebben. De amfipatsche stoffen kunnen met elkaar micellen vormen. Er ontstaat als het ware een bolletje doordat de hydrofobe staarten bij elkaar gaan zitten en de hydrofiele koppen zich naar buiten keren. Deze koppen gaan interacties aan met het water.
De opbouw van een celmembraan ziet er ongeveer hetzelfde uit. Zowel binnen als buiten de cel is een polaire omgeving waar de polaire koppen interacties mee aangaan. De koppen keren zich naar buiten en de apolaire staarten steken naar elkaar toe. Hierdoor ontstaat er een dubbele laag. De cel communiceert met de buitenkant (extracellulaire ruimte) door middel van eiwitten die door de membranen heen steken. Het deel van het eiwit dat zich in het celmembraan bevindt is hydrofoob. De cel bestaat naast 70% water uit 30% chemische stoffen. Dit zijn voornamelijk eiwitten, DNA, RNA, lipiden en suikers, dit zijn macromoleculen. Deze stoffen bestaan uit subunits, die gepolymeriseerd worden en zo lange ketens vormen. Bij eiwitten bijvoorbeeld zijn de subunits de 20 aminozuren. Voor DNA en RNA zijn er 4 nucleotiden. De losse subunits worden met covalente.....read more
Notes bij Gezonde en Zieke Cellen 1 (2014-2015)Deze aantekeningen zijn gebaseerd op 2014-2015
De cel is de kleinste organische eenheid in het lichaam en wordt afgesloten door een membraan. In de cel zitten verschillende organellen (bijvoorbeeld de celkern) met een eigen functie, die ook omhuld worden door een membraan. Door middel van aankleuren kunnen onder de microscoop de verschillende onderdelen van de cel en de aanwezige eiwitten duidelijker zichtbaar worden gemaakt. Cellen zijn heel dynamisch door de eiwitten in de cel. Er zijn verschillende soorten cellen met verschillende vormen en maten. Een spiercel ziet er anders uit dan een epitheelcel.
De cel bestaat voor een groot gedeelte uit water en is een goed oplosmiddel voor polaire stoffen. De mens bestaat voor 70% uit water. Water verdrijft echter vet, een hydrofobe stof. De cel maakt gebruik van amfipathische/amfifiele stoffen, die aan de ene kant een polaire kop en aan de andere kant een apolair (hydrofobe) staart (vetzuur) hebben. De amfipatsche stoffen kunnen met elkaar micellen vormen. Er ontstaat als het ware een bolletje doordat de apolaire staarten bij elkaar gaan zitten en de polaire koppen zich naar buiten keren. Deze gaan interacties aan met het water.
De opbouw van een celmembraan ziet er ongeveer hetzelfde uit. Zowel binnen als buiten de cel is een polaire omgeving waar de polaire koppen interacties mee aangaan. De koppen keren zich naar buiten en de apolaire staarten steken naar elkaar toe. Hierdoor ontstaat er een dubbele laag. De cel communiceert met de buitenkant (extracellulaire ruimte) door middel van eiwitten die door de membranen heen steken. Het deel van het eiwit dat zich in het celmembraan bevindt is hydrofoob.
De cel bestaat naast 70% water uit chemische stoffen. Dit zijn voornamelijk eiwitten, DNA, RNA, lipiden en suikers. Deze stoffen bestaan uit subunits, die gepolymeriseerd worden en zo lange ketens vormen. Bij eiwitten bijvoorbeeld zijn de subunits de 20 aminozuren. Voor DNA en RNA zijn er 4 nucleotiden. De losse subunits worden met covalente bindingen aan elkaar gekoppeld. De eenheden worden aan elkaar gekoppeld onder afsplitsing van water (condensatiereactie). De covalente verbindingen binnen een molecuul kunnen verbroken worden onder invloed van water (hydrolysereactie). De losse moleculen die ontstaan tijdens een condensatiereactiegaan ook een interactie.....read more
Samenvatting week 4 (GZC I)Deze samenvatting is gebaseerd op het studiejaar 2013-2014.
Primaire weefsels in ons lichaam zijn sociale verbanden van cellen die weefsels vormen. Ons lichaam kent vier primaire weefseltypen. De eerste zijn de epithelia: de cellulaire dekweefsels die de buitenkant van het lichaam en alle holten in het lichaam bekleden. Epitheelcellen grenzen heel nauw aan elkaar en zijn met stevige junctions verbonden. Epitheel staat vaak bloot aan slijtage, er is daarom veel celvernieuwing. Darmepitheel is eenlagig epitheel, de epidermis is een meerlagig epitheel.
De tweede groep van weefsels wordt gevormd door de bind- en steunweefsels en bloed. Dit weefsel bestaat uit cellen die in het algemeen omringd worden door een extracellulaire matrix, die zij zelf produceren. Een extracellulaire matrix bestaat uit weefselvloeistof, vezels en andere eiwitten, die door bijvoorbeeld fibroblasten worden gemaakt. Bindweefsel is veel luchtiger weefsel dan epitheel. De cellen zijn niet zo nauw verbonden met elkaar als in epitheel weefsel en communiceren daarom ook anders. Mesenchym: Embryonale term voor bindweefsel.Tot de bind- en steunweefsels behoren ook ons kraakbeen, bloed en onze botten. Het is een familie, omdat de cellen in deze weefsels erg op elkaar lijken met betrekking tot de productie van de belangrijkste extracellulaire matrixcomponenten zoals collageen en elastine. Maar ze zijn toch gespecialiseerd, want in bindweefsel is de extracellulaire matrix veel vloeibaarder dan in been waar het collageen juist voor een harde substantie zorgt.
De derde weefselgroep wordt gevormd door spierweefsel. Dit is onder te verdelen in skeletspierweefsel, hartspierweefsel en glad spierweefsel.
De vierde primaire weefselgroep is het zenuwweefsel. Zenuwweefsel bestaat uit neuronen met lange uitlopers en gliacellen. Tussen de cellen is zeer weinig extracellulaire matrix aanwezig. Zenuwcellen zijn heel specifiek door de lange uitlopers die synaptische contacten met elkaar maken.
Hoe ontstaan de verschillende weefsels in ons lichaam?
Er zijn in ons lichaam 200 verschillende soorten celtypen, die allemaal uit dezelfde embryonale stamcellen ontstaan. Embryonale stamcellen zijn omnipotent, dus kunnen ze aanleiding geven tot het ontstaan van alle mogelijke cellen in ons lichaam.
Verschillen Epitheel en Bindweefsel
Epitheel en bindweefsel zijn elkaars tegenpolen qua weefsels. Ze hebben een verschillend cytoskelet, verschillende vormen van communicatie, een verschillende extracellulaire matrix en een andere manier van bewegen. Alle weefsels bestaan uit cellen en door hen geproduceerde extracellulaire matrix (bevat componenten, zoals eiwitten en vezels). Per weefsel kunnen deze componenten en de hoeveelheid extracellulaire matrix echter sterk verschillen.
Epitheel
Het epitheel weefsel ontstaat uit alle drie de kiembladen. Uit de blastocyst ontstaan drie belangrijke kiembladen: het endoderm (waar je verteringskanaal uit gevormd wordt), het mesoderm (waar je bindweefsel, been, spieren, vetcellen en je bloedvatendotheel gevormd wordt) en het ectoderm (waar je epidermis en je centrale zenuwstelsel uit gevormd wordt). Door deze verschillend oorsprongen.....read more
Samenvatting bij de colleges bij Gezonde & Zieke Cellen 2 (GZC), week 5Deze samenvatting is gebaseerd op het studiejaar 2013-2014.
Er wordt bij deze tumoren onderscheid gemaakt tussen primaire en secundaire tumoren. De primaire tumoren ontstaan vanuit de hersenen, zenuwen en omgevende structuren zelf. Bij de secundaire tumoren gaat het om de metastasen in het zenuwstelsel, waarvan de primare tumor ergens anders in het lichaam is gelegen. De primaire tumoren kennen een incidentie van ongeveer 10 per 100.000 personen en meer dan de helft hiervan is kwaadaardig.
Ook kan er op anatomische gronden een onderverdeling gemaakt worden tussen intrinsieke en extrinsieke tumoren. Intrinsieke tumoren zijn de tumoren die zich binnen de begrenzing van de pia mater bevinden. Het gaat hierbij dus om tumoren die zich bevinden in de grote en kleine hersenen, hersenstam, verlengde merg en ruggenmerg. Deze tumoren gaan uit van zenuwcellen, hun uitlopers, niet-neuronale ondersteunende cellen (gliacellen) en afweercellen, mesenchymale cellen (zoals in de wand van bloedvaten) en metastasen. De extrinsieke tumoren bevinden zich buiten de pia mater en gaan uit van weefsels die het zenuwstelsel omgeven zoals het bot en de hersenvliezen en vanuit de weefsels die niet tot de hersenen gerekend worden, zoals de hypofyse. Weer een andere indeling maakt onderscheid tussen tumoren van het centrale zenuwstelsel aan de ene kant en tumoren van het perifere zenuwstelsel aan de andere kant. De meest voorkomende tumoren zijn de gliomen (neuro-epitheliale tumoren), de tumoren van de perifere zenuwen (schwannomen en neurofibromen), de meningeomen en de metastasen.
Over de pathogenese van primaire hersentumoren is nog maar weinig bekend. Wel bestaat er een relatie tussen het ontstaan ervan en schedelbestraling. Bijna altijd treedt een hersentumor sporadisch op, dus zonder dat er directe aanwijzingen bestaan op een verhoogde kans op hersentumoren in de familie. Wel zijn er enkele erfelijk overdraagbare aandoeningen bekend waarbij er een sterk verhoogd risico op hersentumoren bestaat. Voorbeeld hiervan zijn neurofibromatosis type 1 en 2, de ziekte van Von Hippel-Lindau en het syndroom van Turcot, het syndroom van Li-Fraumeni en het syndroom van Cowden. Er bestaat geen bewijs voor een relatie tussen hersentumoren en elektromagnetische straling afkomstig van telefoons en hoogspanningsmasten.
Hersentumoren
Symptomen van hersentumoren kunnen, op basis van het onderliggende pathofysiologische mechanisme, worden onderverdeeld in drie groepen:
Stoornissen in de prikkelgeleiding van neuronaal weefsel leidend tot epilepsie.
Verstoring van de neuronale functie ten gevolge van compressie of aantasting van neuronaal weefsel. Dit leidt tot ischemie en neurologische uitval.
Verhoging van de intracraniële druk leidend tot symptomen van hoofdpijn, misselijkheid en verschillende graden van bewustzijnsdaling.
Intrinsieke tumoren in het hersenparenchym veroorzaken vaker epileptische verschijnselen dan extrinsieke tumoren. Een eerste epileptische aanval zonder andere neurologische verschijnselen is dan altijd een reden voor verdere diagnostiek. Zowel intrinsieke als extrinsieke.....read more
Samenvatting bij de colleges bij Gezonde & Zieke Cellen 2 (GZC), week 4Deze samenvatting is gebaseerd op het studiejaar 2013-2014.
Het colorectaal carcinoom leidt tot een aanzienlijke mortaliteit in de westerse wereld. Het is de 2e doodsoorzaak ten gevolge van kanker in Nederland, met 10.000 nieuwe gevallen per jaar. De 5-jaarsoverleving is 40-45%. De incidentie zal de komende jaren verder stijgen. Men verwacht dat er in 2015 14.000 nieuwe gevallen zullen zijn. Iedereen heeft een levenslang risico op het colorectaal carcinoom (CRC) van 5-6%.
Een coloncarcinoom ontwikkelt zich uit een poliep. De overgang van poliep naar CRC zal gemiddeld in een periode van 10 tot 15 jaar na het optreden van de poliep plaatsvinden. 30-50% van alle volwassenen in Nederland ontwikkelt adenomateuze poliepen, en ongeveer 10% van deze poliepen zal zich ontwikkelen tot een CRC. In de ontwikkeling van de normale situatie naar een poliep en uiteindelijk naar een carcinoom treden mutaties op in het DNA. Meestal treedt de ontwikkeling van normaal darmslijmvlies naar poliep op door een mutatie in het APC-gen (tumorsuppressorgen). Deze poliep ontwikkelit zich verder tot een carcinoom door een mutatie in het p53 gen(het verlies van apoptose met als gevolg ongeremde groei).
25% van de poliepen komen voor in rectum, 25% in het sigmoïd, 20% in het colon descendens, 10% in het colontransversum, 10% in het colon ascendens en 10% in het caecum. Linkszijdige carcinomen komen dus vaker voor dan rechtzijdige carcinomen. In totaal zijn 70% van de coloncarcinomen linkszijdig.
De kans dat een persoon een poliep ontwikkelt neemt toe met de leeftijd. Ook het voorkomen van coloncarcinoom neemt toe met de leeftijd. Het verwijderen van een poliep leidt tot een reductie in het risico op een CRC. Je verwijderd de afwijking, nog voordat het kanker is geworden. De poliep kan endoscopisch verwijderd worden, dit heet poliepectomie. De manier van verwijderen is afhankelijk van de soort poliep. Wanneer de poliep een duidelijke steel heeft, kan er een metale lis omheen gelegd worden. Vervolgens wordt de steel doorgebrand door stroom door deze lis te laten gaan. De poliep kan vervolgens voor histologisch onderzoek/pathologisch onderzoek worden aangeboden. Wanneer er sprake is van een poliep zonder steel wordt de mucose met behulp van een blauwe kleurstof.....read more
Samenvatting bij de colleges bij Gezonde & Zieke Cellen 2 (GZC), week 3Deze samenvatting van de colleges is gebaseerd op het studiejaar 2013-2014.
Van de urologische tumoren komt prostaatkanker het meest voor. In de onderstaande tabel staan de urologische tumoren op volgorde van voorkomen.
Tumor | Soort | Incidentie |
Prostaatkanker | Adenocarcinoom | 10.000 |
Blaaskanker | Overgangsepitheelcarcinoom | 4500 |
Nierkanker | Niercelcarcinoom | 1500 |
Testistumoren | Kiemceltumoren | 600 |
Peniskanker | plaveiselcelcarcinoom | 120 |
Een prostaat heeft ongeveer de grootte van een walnoot en weegt ongeveer 20-25 gram. Vaak zal de prostaat bij oudere mannen vergroten. Dit verschijnsel wordt benigne prostaat hyperplasie genoemd. Er kunnen dan obstructieve en irritatieve klachten ontstaan. Onder obstructieve klachten vallen: moeite met op gang komen (hesitatie), slappe straal, onderbroken mictie, gevoel niet helemaal leeg te plassen. Onder irritatieve klachten vallen: toegenomen frequentie mictie (vaker dan om de 2 uur), imperatieve drang (moeite om uit te stellen) en nycturie (’s nachts naar de wc moeten).
Andere oorzaken waarbij deze klachten van de lagere urinewegen kunnen ontstaan zijn: sclerose van de blaashals, strictuur van de urethra of meatus urethra stenose.
De prostaat bestaat uit een centraal gebied met fibreus weefsel en een perifeer gebied met vooral klierbuisjes. Deze klierbuisjes maken vloeistoffen die in de urethra kunnen worden uitgestoten (bijmenging voor bevruchting). Bij vergroting van de prostaat zal de urethra vernauwen. Hierdoor moet de blaas meer kracht leveren om de urine te lozen. Er ontstaat blaashypertrofie. Later kan urineretentie ontstaan.
Er is een centrale zone, een perifere zone, een transitionele zone of peri-urethrale zone en een anterieure zone. Carcinomen ontwikkelen zich met name in de perifere zone. Hierdoor ontbreken bij carcinomen in eerste instantie de mictie klachten. Er is niet direct obstructie van de urethra. In een later stadium kan dit echter wel optreden. In de transitionele zone ontstaat met name hyperplasie.
Wanneer een patiënt zich op het spreekuur meld met klachen van de lagere urine wegen kunnen de volgende testen zinvol zijn:
Urine sediment/kweek
Rectaal toucher
Plasdagboek
Flow meting en residu na meting
Samenvatting week 2 (GZC I)Deze samenvatting is gebaseerd op het studiejaar 2013-2014.
De cel is de kleinste eenheid van leven. Er zijn veel verschillende cellen (ca. 200) in ons lichaam. De mens heeft ongeveer 1x1014 cellen. De cel vormt een onderdeel van het organismen. Terwijl er ook organismen zijn die uit slechts één cel bestaan, denk aan bacteriën, schimmels, gisten en parasieten. Celbiologie is belangrijk, omdat je moet weten hoe een gen tot een genproduct leidt in zijn natuurlijke omgeving (de cel). Op die manier is te achterhalen waar een storing (mutatie) zit en zo de mogelijke oorzaak van een ziekte opsporen om er vervolgens geneesmiddelen tegen te ontwikkelen. Cellen zijn heel dynamisch. Zij kunnen zich bewegen en zijn ook in staat om te eten, denk daarbij aan een macrofaag die een bacterie opeet. Verder zijn ze in staat te reproduceren, te communiceren en dood te gaan. De cellen kunnen zichtbaar worden gemaakt met behulp van een microsoop. Er zijn verschillende soorten microscopen, waaronder de lichtmicroscoop. Om in een cel te kunnen kijken en de organellen goed te zien is een elektronenmicroscoop nodig. Onder een elektronenmicroscoop kunnen echter geen levende cellen bekeken worden.
Organellen vormen membraanomgeven eilandjes in de cel met een eigen micro-milieu en specifieke functie. Ze worden gevormd en in stand gehouden door een constante aanvoer van nieuwe eiwitten. Transport van nieuw aangemaakte eiwitten naar het juiste organel is van levensbelang voor de cel. Een aantal onderdelen van de cel zijn:
Cytosol: gelachtige basissubstantie van de cel
Cytoplasma=cytosol + organellen
Celkern (nucleus): bevat DNA en wordt omgeven door een kernenvelop. De kern speelt een rol bij de aanmaak van mRNA en vormt de opslagplaats voor het genetisch materiaal.
Transport van eiwitten die naar de kern moeten
De kern is helemaal omgeven door een dubbel membraan waarin zich poriën bevinden. Deze kanaaltjes spelen een rol bij het transport van stoffen de kern in en uit. De nucleaire lamina die net onder de binnenste kernmembraangelegen, zorgen voor stevigheid. Een klein deel van de eiwitten die in de het cytosol geproduceerd worden,is bestemd voor de kern. Het eiwit zelf bevat een codein hun aminozuurvolgorde die de informatie bevat voor de eindbestemming. In het geval dat het eiwit naar de kern moet, bevat het een code, genaamd nuclear localization signal. Door een receptoreiwit, nuclear transport receptor, wordt deze code herkend. De receptor kan aan het eiwit binden en zo komt het eiwit via een kernporie de kern binnen. Ran-GTP (schakelaar) bindt aan het eiwitcomplex en verdringt daarmee het kerneiwit uit de receptor. De receptor gebonden aan het GTP gaan uit de kern.In het cytosol wordr GTP naar.....read more
Samenvatting week 1 (GZC I)Deze samenvatting is gebaseerd op het studiejaar 2013-2014.
De cel is de kleinste organische eenheid in het lichaam en wordt afgesloten door een membraan. In de cel zitten verschillende organellen (bijvoorbeeld de celkern) met een eigen functie, die ook omhuld worden door een membraan. Door middel van aankleuren kunnen onder de microscoop de verschillende onderdelen van de cel en de aanwezige eiwitten duidelijker zichtbaar worden gemaakt. Cellen zijn heel dynamisch door eiwitten die dit veroorzaken.
De cel bestaat voor een groot gedeelte uit water en is een goed oplosmiddel voor polaire stoffen. De mens bestaat voor 70% uit water. Water verdrijft echter vet, een hydrofobe stof. De cel maakt gebruik van amfipathische/amfifiele stoffen, die aan de ene kant een polaire kop en aan de andere kant een apolair (hydrofobe) staart (vetzuur) hebben. . De amfipatsche stoffen kunnen met elkaar micellen vormen. Er ontstaat als het ware een bolletje doordat de apolaire staarten bij elkaar gaan zitten en de polaire koppen zich naar buiten keren. Deze gaan interacties aan met het water,
De opbouw van een membraan om de cel ziet er ongeveer hetzelfde uit. Zowel binnen als buiten de cel is een polaire omgeving waar de polaire koppen interacties mee aangaan. De koppen keren zich naar buiten en de apolaire staarten steken naar elkaar toe. Er ontstaat een dubbele laag. De cel communiceert met de buitenkant (extracellulaire ruimte) door middel van eiwitten die door de membranen heen steken. Het deel van het eiwit dat zich in het celmembraan bevindt is hydrofoob.
De cel bestaat naast 70% water uit chemische stoffen. Dit zijn voornamelijk eiwitten, DNA, RNA, lipiden en suikers. Deze stoffen bestaan uit subunits, die gepolymeriseerd worden en zo lange ketens vormen. Bij eiwitten bijvoorbeeld zijn de subunits de 20 aminozuren. Voor DNA en RNA zijn er 4 nucleotiden. De losse subunits worden met covalente bindingen aan elkaar gekoppeld. De ontstane ketens vormen een molecuul. De losse moleculen gaan ook een interactie met elkaar aan door middel van non-covalente bindingen.
Eiwitten
Een aminozuur bestaat uit een centraal C-atoom, een carboxylgroep en een aminogroep. Aan het centrale C-atoom zit een specifieke zijketen. Deze zijketens hebben een verschillend karakter, zoals hydrofoob, hydrofiel, zuur, base. Deze specificiteit van de zijketens zorgt uiteindelijk voor de eigenschappen van een eiwit. De aminozuurvolgorde is gecodeerd in het DNA. Het vormt de primaire structuur van een eiwit.
De aminozuren worden door peptidebindingen (covalente bindingen) aan elkaar gekoppeld. De peptidebinding is stijf en vlak, dus niet vrij draaibaar. Tussen de carboxylgroep en de aminogroep ontstaat namelijk een soort dubbele binding, doordat.....read more
Samenvatting week 5 (GZC I)Deze samenvatting is gebaseerd op het studiejaar 2013-2014.
Een primaire tumor ontstaat op een bepaalde locatie en is vaak goed behandelbaar. Een secundaire tumor ontstaat na metastase. De kankercellen van de primaire tumor verspreiden zich door het lichaam, waar door er ook op andere plekken tumoren ontstaan.. Een tumor ontstaat uit 1 cel. Deze cel is vaak een stamcelachtige cel. De kankercel ontstaat door een bepaalde mutatie, die ervoor zorgt dat een stamcel alleen maar dochtercellen produceert die zich niet differentiëren, maar alleen maar blijven delen. Deze cellen zijn pluripotent. Een andere optie is dat deze stamcel alleen maar stamcellen als dochtercellen produceert. Het gevolg is een ongeremde groei, waardoor een tumor ontstaat.
Er zijn twee soorten tumoren, goedaardige (= beligne) en kwaadaardige (=maligne). Het verschil daartussen is dat de kwaadaardige tumor in het omringende weefsels infiltreert en niet meer gelokaliseerd is. Behandeling is veel moeilijker, omdat de kankercellen door het lichaam worden verspreid via de bloedvaten en/of lymfevaten. Hierdoor ontstaan er op verschillende plaatsen tumoren. De weg naar een metastaserende tumorcel is als volgt. Eerst is het een beginnende, goedaardige tumorcel. Deze gaat zich veelvuldig delen, waardoor een goedaardige tumorcel ontstaat. Nu ontstaat er in een of meerdere cellen een mutatie waardoor ze door de basale lamina heen kunnen dringen. Zij produceren bepaalde enzymen die de basale lamina plaatselijk afbreken, waardoor de tumorcellen in het onderliggen weefsel kunnen infiltreren. Om zich verder te kunnen verspreiden moeten deze cellen in staat zijn hun junctions los te laten en moeten zich kunnen bewegen door het bindweefsel. Als dit het geval is kunnen deze cellen ook in debloedvaten of de lymfevaten infiltreren. Wanneer de kankercellen in staat zijn afweerreacties te ontwijken, kunnen zij zich op andere plaatsen in het lichaam vestigen. Er treedt extravasatie op, dit is uittreding van kankercel buiten de vaten en angiogenese (groei bloed –en lymfevaten). Hierdoor kan er een nieuwe tumor ontstaan op een andere plek.
Een tumorcel bestaat niet alleen uit kankercellen, maar daarnaast ook uit immuun cellen, fibroblasten (cancer assistent fibroblasts) en endotheelcellen. Deze gaan een interactie met elkaar aan binnen de tumor waardoor een zeer complex geheel ontstaat. Zo zorgen de fibroblasten in een tumor er voor dat er bloedvaten worden gevormd, zodat de kankercellen worden voorzien in voedingsstoffen en zuurstof. Ook onderdrukken zij het immuunsysteem.
Helaas zijn veel tumoren pas in een laat stadium te ontdekken. Er zijn al ongeveer 108 cellen ontstaan (diameter ± 5 mm), voordat de tumor zichtbaar is in de X-ray. Vervolgens is een tumor bij ongeveer 109 cellen voelbaar (diameter ± 20-50 mm) en al bij 1012 cellen gaat de patiënt dood. Doordat tumoren pas in een laat stadium worden ontdekt, past men zeer agressieve therapieën toe, namelijk snijden, branden (radiotherapie) en vergiftigen (chemotherapie). Het.....read more
Samenvatting literatuur - Van cel tot molecuul - Geneeskunde UL - 2016/2017Deze samenvatting is gebaseerd op collegejaar 2016-2017.
Deze samenvatting (deel 1 en deel 2) is te gebruiken bij alle verplichte hoofdstukken uit de volgende boeken voor het vak Van Cel tot Molecuul:
Essential Cell Biology van Alberts et al uit 2014, namelijk onderwerpen uit hoofdstukken
3, 4, 5, 6, 7, 9, 10, 11, 12, 15, 16, 17, 18, 19.
Elements of Medical Genetics van Turnpenny uit 2011, namelijk onderwerpen uit hoofdstukken
1, 2, 3, 6, 7, 8, 9, 17, 18, 22
Medical Physiology: A Cellular And Molecular Approach van Boron & Boulpaep uit 2008, namelijk hoofdstuk 2
Voordat een enzym een reactie kan katalyseren moet het enzym eerst binden aan zijn substraat. Vervolgens wordt er een product aangemaakt dat bindt aan het enzym. Wanneer dit product losraakt van het enzym kan er een volgend substraat binden. De gekatalyseerde reacties van een substraat dat een bepaald product vormt, verschillen in snelheid. De snelheid kan gemeten worden in een experiment waarbij zuivere enzymen en substraten gemixt worden onder zorgvuldige omstandigheden. Als alle enzymen gebonden zijn door substraat, is de Vmax bereikt.
De substraatconcentratie die nodig is om een enzym efficiënt te laten werken, wordt vaak gemeten met een andere parameter: Km. De Km is de substraatconcentratie waarbij het enzym op de helft van zijn maximale snelheid werkt (0,5 Vmax).
Wanneer een enzym de activeringsenergie voor de reactie Y naar X verlaagt, wordt tegelijkertijd ook de activeringsenergie voor de reactie X naar Y verlaagd met precies dezelfde hoeveelheid.
Het bestuderen van de kinetica (bewegingsleer) van een enzym (hoe snel het opereert, hoe het zich gedraagt tegenover het substraat, hoe de activiteit wordt gecontroleerd), zorgt ervoor dat we kunnen voorspellen hoe een individuele katalysator.....read more
Aanvulling Samenvatting van Cel tot Molecuul Alberts blz 372-377Deze samenvatting is geschreven in collegejaar 2012-2013.
Thema 2.A.3 Abnormale Celgroei week 13Deze samenvatting is gebaseerd op collegejaar 2012-2013. Bekijk hier ons huidige aanbod.
Thema 2.A.3 Abnormale Celgroei week 12Deze samenvatting is gebaseerd op collegejaar 2012-2013. Bekijk hier ons huidige aanbod.
Thema 2.A.2 Abnormale celgroei week 6Deze samenvatting is gebaseerd op collegejaar 2012-2013. Bekijk hier ons huidige aanbod.
Summary: Essential Cell Biology (Alberts et al) - First partThis summary is based on the 3rd edition of Essential Cell Biology from Alberts et al. The remaining chapters can be accessed when logged in and can be found here: Second part of the summary
Cells are the fundamental units of life; all living things are made of cells. The present-day cells are believed to have evolved from an ancestral cell that excited more than 3 billion years age. Cells vary enormous in appearance and function, however all living cells have a similar basic chemistry.
With the invention of the microscope, it became clear that plants and animals are assemblies of cells, that cells can also exist as independent organisms, and that cells individually are living in the sense that they can grow, reproduce, convert energy from one form into another, respond to their environment, and so on. Although cells are varied when viewed from the outside, all living things are fundamentally similar inside. And in all living things, genetic instructions, called genes, are stored in DNA molecules. In every cell, the instructions in the DNA are read out, or transcribed, into a chemically related set of molecules made of RNA. The messages carried by the RNA molecules are in turn translated into yet another chemical form: they are used to direct the synthesis of a huge variety of large protein molecules that dominate the behaviour of the cell. In sum, the reproduction process exists of replication (DNA synthesis), transcription (RNA synthesis) and translation (protein synthesis). Unfortunately, the copying of DNA is not always perfect, and the instructions are occasionally corrupted. Later is this summary we will discuss this further.
Cells are enclosed by a plasma membrane that separates the inside of the cell from the environment. And all cells contain DNA as a store of genetic information and use it to guide the synthesis of proteins. Cells in a multicellular organism, though the all contain the same DNA, can be very different. They use their genetic information to direct their biochemical activities according to cues they receive from their environment.
Cells of animal and plant tissues are typically 5-20 micrometer in diameter and can be seen with a light microscope, which also reveals some of their internal components (organelles). The electron microscope permits the smaller organelles and even individual molecules to be seen, but specimens require elaborate preparation and cannot be viewed alive. So, the invention of the light microscope led to.....read more
Summary: Essential Cell Biology (Alberts et al) - Second partThis summary is based on the 3rd edition of Essential Cell Biology from Alberts et al. The first 10 chapters are open access and can be found here: First part of the summary
Cell membranes enable a cell to create barriers that confine particular molecules to specific compartments. The simplest bacteria have only a single membrane, the plasma membrane. Eucaryotic cells, however, contain in addition a profusion of internal membranes that enclose intracellular compartments. All cell membranes are composed of lipids and proteins and share a common general structure. The lipid component consists of many millions of lipid molecules forming a lipid bilayer. This lipid bilayer gives the membrane its basic structure and serves as a permeability barrier.
The lipids in cell membranes combine two very different properties in a single molecule: each lipid has a hydrophilic (‘water-loving’) has and one or two hydrophobic (‘water-hating’) hydrocarbon tails. There are three major classes of membrane lipid molecules:
The most abundant lipids in cell membranes are phospholipids, and the most common type of phosphoslipid in most cell membranes is phosphatidylcholine. Molecules with both hydrophilic and hydrophobic properties are termed amphipathic. This chemical property plays a crucial part in driving these lipid molecules to assemble into bilayers. They assemble spontaneously into bilayers when placed in water, forming closed compartments that reseals of torn.
Amphipathic molecules re subject to two conflicting forces: the hydrophilic head is attracted to water, while the hydrophobic tail shuns water and seeks to aggregate with other hydrophobic molecules. This conflict is resolved by the formation of a lipid bilayer, because the hydrophilic heads face the water at each of the two surfaces of the sheet of molecules and the hydrophobic tails are all shielded from the water and lie next to one another in the interior of this ‘sandwich’. Finally, the phospholipid bilayers spontaneously close in on themselves to form sealed compartments.
The lipid bilayer is fluid, and individual lipid molecules are able to diffuse within their own monolayer; they do not, however, spontaneously flip from one monolayer to the other. The two layers of the lipid bilayer have different lipid compositions, reflecting the different functions of the two faces of a cell membrane.
The fluidity of a cell membrane (the ease with which its lipid molecules move within the plane of the bilayer) is important for membrane function and has to be
.....read more Thema 2.A.2 Abnormale celgroei week 7Deze samenvatting is gebaseerd op collegejaar 2012-2013. Bekijk hier ons huidige aanbod.
Study Notes bij Van Mens tot Cel - Geneeskunde UL (2015-2016)Deze aantekeningen zijn gebaseerd op 2015-2016
Anatomie is van belang voor het uitvoeren van lichamelijk onderzoek. De oppervlakte anatomie is de ‘projectie op de lichaamswand’: je moet aan kunnen wijzen welke organen er op welke plek onder de huid zitten.
Anatomie is van belang bij :
De (algemene) bouw van organen in relatie tot hun functie
Samenhang van organen en orgaansystemen
Lichamelijk onderzoek: projectie van organen
Interpretatie van MRI, röntgen, CT opnamen enzovoort
We houden ons dit blok bezig met het aanleren van de algemene lichaamsbouw op verschillende niveaus:
Macroscopisch niveau: met het blote oog zichtbaar.
Microscopisch niveau: te zien met de microscoop
histologie (weefselleer) en cytologie (celleer).
Hierbij staat de relatie tussen een normale en afwijkende bouw en de betekenis hiervan voor het wel of niet juist functioneren van de organen en orgaansystemen centraal. Het doel van het bestuderen van de anatomie is om delen van het menselijk lichaam te leren herkennen, en om op die manier het geheel te kunnen begrijpen.
Study Notes bij Van Mens tot Cel - Geneeskunde UL (2013-2014)Deze aantekeningen zijn gebaseerd op 2013-2014
HC Bouwplan: van mens tot cel (21 oktober 2013)
We houden ons dit blok bezig met het aanleren van de algemene lichaamsbouw op verschillende niveaus:
Macroscopisch niveau (met het blote oog zichtbaar).
Microscopisch niveau (te zien met de microscoop): histologie (weefselleer) en cytologie (celleer).
Hierbij staat de relatie tussen een normale en afwijkende bouw en de betekenis hiervan voor het wel of niet juist functioneren van de organen en orgaansystemen centraal. Het doel van het bestuderen van de anatomie is om delen van het menselijk lichaam te leren herkennen en om op die manier lichamelijk processen te begrijpen.
Thema’s
We werken dit blok aan de hand van verschillende thema’s. De eerste drie thema’s zijn bouwplan en ontwikkeling, de huid en het bewegingsstelsel. Bij het eerste thema gaan we in op de systematische anatomie, waarbij het lichaam is ingedeeld in orgaansystemen. We behandelen onder andere het ademhalingssysteem, bewegingssysteem, zenuwstelsel en circulatiestelsel. Bij de ontwikkeling gaan we in op het tot stand komen van de bouw. We gaan het er ook over hebben dat er veel mis kan gaan tijdens de ontwikkeling en over wat de sensitieve perioden zijn.
Vanaf thema 4 houden we ons bezig met de topografische anatomie: het deel van de anatomie dat het lichaam opdeelt in regio’s. De thema’s zijn borst, buik & bekken en hoofd & hals. We gaan in op de medische beeldvormende technieken waardoor we organen leren herkennen. De oppervlakte anatomie is de ‘projectie op de lichaamswand’: je moet aan kunnen wijzen welke organen er op welke plek onder de huid zitten. Dit is later van belang voor het uitvoeren van lichamelijk onderzoek.
Onderwijsvormen
Een KVC is een Klinisch Verdiepingscollege. Hierin wordt aangegeven hoe we in de kliniek gebruik kunnen maken van onze anatomische kennis.
Er zijn veel hoorcolleges waarin de stof aangeboden wordt die niet duidelijk in de kernboeken verwoord wordt, of waarin klinische verdieping wordt geboden. Ook is er elke week een Responsie College. Het is belangrijk dat je goed voorbereid naar een hoorcollege komt. Van tevoren kun je je vraag posten op het discussion board op blackboard.
Naast de colleges zijn er opdrachten die je moet maken en is er elke week een werkgroep. Daarbij zijn er deze periode practica: die zijn verplicht en mag je niet missen. Ook zijn er een aantal COO: Computer Ondersteunend Onderwijs. Als er op blackboard in het themamapje een COO staat, is dit verplicht om te maken. De COO die niet in het blokboek staan zijn de quizzen. Onder het mapje ‘overige COO’ vind je de niet-verplichte COO waar je door middel van spelletjes de anatomische kennis kunt testen.
Preclass toetsen zijn toetsen waarin je vragen.....read more
Study Notes bij Van Mens tot Cel - Geneeskunde UL (2014-2015)Deze aantekeningen zijn gebaseerd op 2014-2015.
We houden ons dit blok bezig met het aanleren van de algemene lichaamsbouw op verschillende niveaus:
Macroscopisch niveau: met het blote oog zichtbaar.
Microscopisch niveau: te zien met de microscoop: histologie (weefselleer) en cytologie (celleer).
Hierbij staat de relatie tussen een normale en afwijkende bouw en de betekenis hiervan voor het wel of niet juist functioneren van de organen en orgaansystemen centraal. Het doel van het bestuderen van de anatomie is om delen van het menselijk lichaam te leren herkennen, en om op die manier het geheel te kunnen begrijpen.
Thema’s
We werken dit blok aan de hand van verschillende thema’s. De eerste drie thema’s zijn bouwplan en ontwikkeling, de huid en het bewegingsstelsel. Bij het eerste thema gaan we in op de systematische anatomie, waarbij het lichaam is ingedeeld in orgaansystemen. We behandelen onder andere het ademhalingssysteem, bewegingssysteem, zenuwstelsel en circulatiestelsel. Bij de ontwikkeling gaan we in op het tot stand komen van de bouw. We gaan het er ook over hebben dat er veel mis kan gaan tijdens de ontwikkeling en over wat de sensitieve perioden zijn.
Vanaf thema 4 houden we ons bezig met de topografische anatomie: het deel van de anatomie dat het lichaam opdeelt in regio’s. De thema’s zijn borst, buik en bekken, en hoofd en hals. We gaan in op de medische beeldvormende technieken waardoor we organen leren herkennen. De oppervlakte anatomie is de ‘projectie op de lichaamswand’: je moet aan kunnen wijzen welke organen er op welke plek onder de huid zitten. Dit is later van belang voor het uitvoeren van lichamelijk onderzoek.
Onderwijsvormen
Een KVC is een Klinisch Verdiepings College. Hierin wordt aangegeven hoe we in de kliniek gebruik kunnen maken van onze anatomische kennis.
Er zijn veel hoorcolleges waarin de stof aangeboden wordt die niet duidelijk in de kernboeken verwoord wordt, of waarin klinische verdieping wordt geboden. Ook is er elke week een Responsie College. Het is belangrijk dat je goed voorbereid naar een hoorcollege komt. Van tevoren kun je je vraag posten op het discussion board op blackboard.
Naast de colleges zijn er opdrachten die je moet maken en is er elke week een werkgroep. Daarbij zijn er deze periode practica: die zijn verplicht en mag je niet missen. Ook zijn er een aantal COO: Computer Ondersteunend Onderwijs. Als er op blackboard in het themamapje een COO staat, is dit verplicht om te maken. De COO die niet in het blokboek staan zijn de quizzen. Onder het mapje ‘overige COO’ vind je de niet-verplichte COO waar je door middel van spelletjes de anatomische kennis kunt testen.
Preclass toetsen zijn toetsen waarin je vragen krijgt over bepaalde onderwerpen.....read more
Study Notes bij Van cel tot molecuul - Geneeskunde UL (2013-2014)Deze aantekeningen zijn gebaseerd op 2013-2014.
Tijdens dit blok komen er twee basisvakken en één klinisch vak ten sprake. Moleculaire celbiologie, genetica en klinische genetica. Tijdens dit blok wordt er gewerkt aan de competenties AWV en gezondheidsbevordering. De twee coördinatoren van dit blok zijn Prof M. Breuning en Prof T. Raap.
Dit blok bevat zeven thema’s.
1. Humane Genoom en Chromosomen
2. Mono genetische Ziekten en Overervingspatronen
3. Replicatie, Transcriptie, Repair en Recombinatie
4. Translatie en Structuur/Functie van Eiwitten
5. Metabolisme en Enzymologie
6. Membranen en Transportprocessen
7. Communicatie en Signaaloverdracht
Bij elk thema hoort een werkgroep en twee studieopdrachten. Bij elke SO-2 worden er 2 studenten uitgekozen die de casus moeten presenteren. Ook moeten zij een verslag over die casus maken. Dit verslag moet schriftelijk ingeleverd worden tijdens de werkgroep, gemaild worden naar de werkgroep docent en online ingevoerd worden in TurnItin (via blackboard). Je moet goed voorbereid naar de werkgroep komen en je kernboeken meenemen. Het verslag wat je samen met een medestudent inlevert moet beoordeelt worden met een voldoende of goed. Wanneer het verslag met een onvoldoende beoordeelt is wordt het tentamencijfer van cel tot molecuul niet vrijgegeven.
Toetsing
Op vrijdag 20 december is er een deeltentamen. Dit deeltentamen gaat over de thema’s 1 tot en met 4. Het bestaat uit 35 meerkeuzenvragen en duurt 2 uur lang.
Het eindtentamen op 17 januari gaat over alle 7 thema’s.
Nucleotiden zijn de bouwstenen van het DNA. DNA bestaat uit een suikermolecuul, fosfaatgroep en een stikstofbase (guanine etc.). Deze structuur is hiernaast weergegeven. De fosfaatgroep is negatief geladen.
Een DNA-streng heeft een 5’ en een 3’ kant. Nieuwe nucleotiden bevinden zich aan de 3’ kant. Het DNA-molecuul bestaat uit een dubbele helix, dus uit 2 DNA strengen. Deze strengen zijn doormiddel van waterstofbruggen aan elkaar geketend. Tussen T en A 2 waterstofbruggen en tussen G en C 3. Bij de aanmaak van nieuw DNA wordt 1 streng gebruikt als matrijsstreng.
Het menselijk DNA kent 3 miljard basenparen, 22000 genen, 1 m lengte, 2nm dik, 3 picogram zwaar en kent 22 autosomen chromosomen en 2 geslachtschromosomen.
Spermacellen en eicellen zijn haploïd en een lichaamscel is diploïd. DNA zit verpakt in chromatine. Er zijn twee soorten chromatine: heterochromatine en euchromatine. Heterochromatine is donker, gecondenseerd, niet actief en er vindt geen DNA transcriptie plaats. Euchromatine is licht van kleur, is actief en er vindt transcriptie plaats. Een cel met een grote kern bevat meer euchromatine aangezien er meer chromatine actief zijn.
DNA is negatief geladen. DNA bindt met positief geladen histonen om een chromatine te vormen.
Allereerst windt.....read more
Study Notes bij Van cel tot molecuul - Geneeskunde UL (2015-2016)Deze aantekeningen zijn gebaseerd op collegeweek 1 t/m 5 van het studiejaar 2015-2016.
Tijdens dit blok komen er twee basisvakken en één klinisch vak ten sprake. Moleculaire celbiologie, genetica en klinische genetica. Tijdens dit blok wordt er gewerkt aan de competenties AWV en gezondheidsbevordering. De twee coördinatoren van dit blok zijn Prof M. Breuning en Prof T. Raap.
Dit blok bevat zeven thema’s.
1. Humane Genoom en Chromosomen
2. Mono genetische Ziekten en Overervingspatronen
3. Replicatie, Transcriptie, Repair en Recombinatie
4. Translatie en Structuur/Functie van Eiwitten
5. Metabolisme en Enzymologie
6. Membranen en Transportprocessen
7. Communicatie en Signaaloverdracht
Bij elk thema hoort een werkgroep en twee studieopdrachten. Bij elke SO-2 worden er 2 studenten uitgekozen die de casus moeten presenteren. Ook moeten zij een verslag over die casus maken. Dit verslag moet schriftelijk ingeleverd worden tijdens de werkgroep, gemaild worden naar de werkgroep docent en online ingevoerd worden in TurnItin (via blackboard). Je moet goed voorbereid naar de werkgroep komen en je kernboeken meenemen. Het verslag wat je samen met een medestudent inlevert moet beoordeelt worden met een voldoende of goed. Wanneer het verslag met een onvoldoende beoordeelt is wordt het tentamencijfer van cel tot molecuul niet vrijgegeven.
Het deeltentamen gaat over de thema’s 1 tot en met 4. Het bestaat uit 35 meerkeuzenvragen en duurt 2 uur lang.
Het eindtentamen gaat over alle 7.....read more
Study Notes bij Van cel tot molecuul - Geneeskunde UL (2014-2015)Deze aantekeningen zijn gebaseerd op collegeweek 2 t/m 5 van het studiejaar 2014-2015.
Nucleotiden zijn de bouwstenen van het DNA. DNA bestaat uit een suikermolecuul (desoxyribose), fosfaatgroep en een stikstofbase (guanine etc.). De fosfaatgroep is negatief geladen. Een DNA-streng heeft een 5’ en een 3’ kant: polariteit. Nieuwe nucleotiden worden aan de 3’ kant aangezet. In losse vorm zit bij RNA een H-groep en bij DNA OH-groep aan 3'. De fosfaatgroep zit aan 5' en de base aan 1'. Het DNA-molecuul bestaat uit een dubbele helix, dus uit 2 DNA strengen. Deze strengen zijn doormiddel van waterstofbruggen aan elkaar geketend. Tussen T en A 2 waterstofbruggen en tussen G en C 3. Bij de aanmaak van nieuw DNA wordt 1 streng gebruikt als matrijsstreng.
Het menselijk DNA kent in 3 miljard basenparen, 22000 genen, 1 m lengte, 2nm dik, 3 picogram zwaar en kent 22 autosomen chromosomen en 2 geslachtschromosomen. Dit is voor haploïde situatie. Spermacellen en eicellen zijn haploïd en een lichaamscel is diploïd. DNA zit verpakt in chromatine. Er zijn twee soorten chromatine: heterochromatine en euchromatine. Heterochromatine is donker, gecondenseerd, niet actief en er vindt geen DNA transcriptie plaats. Euchromatine is licht van kleur, is actief en er vindt transcriptie plaats. Bij euchromatine is het DNA gedecondenseerd zodat enzymen en polymerasen er beter bij kunnen. Een cel met een grote kern bevat meer euchromatine aangezien er meer chromatine actief zijn.
DNA is negatief geladen. DNA bindt met positief geladen histonen om een chromatine te vormen.Allereerst windt het DNA zich om de histonen (2x4 eiwitten) dit vormt een
nucleïosoom. Vervolgens condenseert dit verder met behulp van een 5e histon om een chromatine fiber te vormen. Die fibers maakt dan nog loops en die loops worden gecondenseerd met als resultaat het interfase chromosoom. De meest gecondenseerde vorm van chromatine is in de metafase. Een chromosoom is vaak in de metafase afgebeeld.
Een chromosoom bestaat uit 2 chromatiden. Het punt waarop deze chromatiden aan elkaar zitten wordt het centromeer genoemd. De uiteinden van de chromosoom/chromatiden noemt men het telomeer. Wanneer het centromeer zich niet exact in het midden bevindt (submetacentrisch), heeft de chromosoom lange (Q-armen) en korte (P-armen) armen. Overigens wordt ook bij chromosomen waarbij de armen evenlang zijn (metacentrisch) P en Q armen benoemd. Dit is om onderscheid te maken en zo genlocaties te kunnen aanduiden. Hele kleine armen noemt men satelliet armen. Dit komt voor bij acrocentrische chromosomen
Chromosomen worden geclassificeerd op lengte en op de positie van het centromeer. Wanneer hieruit geen onderscheidt kan worden gemaakt wordt er gekeken naar de G-banding van de chromosoom. Deze G-banding vindt plaats in de metafase met behulp van Giemsa, vervolgens krijgt het chromosoom een uniek licht-donker bandpatroon. Dit noemt men karyotyping, een.....read more
TentamenTests bij Van Mens tot Cel - Geneeskunde UL - #1Bevat een blokspecifiek oefententamen met antwoorden uit voorgaande collegejaren.
A: Epidermis
B: Dermis
C: Hypodermis
A: Colon ascendens
B: Colon sigmoideus
C: Rectum
D: Duodenum
A: Connexine
B: Integrine
C: Cadherine
D: Claudine
A: Fibroblast
B: Neutrofiele granulocyt
C: Osteoprogenitor cel
D: Chondroblast
A: Trophoblast
B: Epiblast
C: Decidua
D: Allantois
A: Cysteine
B: Methionine
C: Proline
D: Glycine
A: Gestoorde passage van de voedselbolus
B: Nasale regurgitatie
C: Aspiratie
D: Reflux van de maaginhoud
A: Een kieuwboog afwijking
B: Een uiting van een vergrote lymfeknoop
C: Een aanlegstoornis van de schildklier
D: Een maligne aandoening met vochtholte
A: 6e
.....read more
TentamenTests bij Cel tot Molecuul - Geneeskunde ULBevat een blokspecifiek oefententamen met antwoorden uit voorgaande collegejaren.
1. Hans en Tineke willen graag een kindje. Zowel de ouders van Hans als de ouders van Tineke zijn beide drager van een autosomaal recessieve ziekte. Wat is de kans dat Hans en Tineke een gezond kind krijgen?
A: 1:4
B: 1:8
C: 1:16
D: 1:32
E: 1:64
2. Merel is een gezonde 26-jarige vrouw. Haar vader heeft daarentegen een dominante erfelijke aandoening, die zich al op kinderleeftijd uit. Merel vraagt zich af hoe groot de kans is dat zij draagster is van dit dominante gen. Deze kans is:
A: 0%
B: 25%
C: 33%
D: 50%
3. Kleurenblindheid heeft een X-chromosomale overerving. De prevalentie van kleurenblindheid is onder de Nederlandse-mannen 4%. Het percentage Nederlandse-vrouwen dat homozygoot is voor deze genen zou rond de … liggen:
A: 0,16%
B: 0,2%
C: 0,8%
D: 1,6%
4. Angelos komt bij de huisarts. Hij maakt zich zorgen, aangezien zijn zus vorige week is overleden aan een aandoening die autosomaal recessief overerft. Voor zover Angelos weet is zijn zus de eerste in de familie waarbij deze ziekte tot uiting kwam. Angelos heeft op dit moment een kinderwens en vraagt de arts hoe groot de kans is dat zijn kind het zieke gen bevat, deze kans bedraagt:
A: 1:3
B: 1:6
C: 1:8
D: 1:12
5. Een vrouw met het syndroom van down is zwanger. Hoe groot is de kans dat dit kindje ook het syndroom van down krijgt? (de kans dat de meiose bij haar partner fout gaat is verwaarloosbaar).
A: 0%
B: 33%
C: 50%
D: 75%
6. Nancy en Robert hebben beide het syndroom van Down. Zij hebben een kinderwens. Hoe groot is de kans dat zij een kindje krijgen met het syndroom van Down?
A: 0 - 12,5%
B: 12,5 - 25%
C: 25 - 50%
D: >50%
7. Susan komt bij de huisarts en verteld dat haar broer vorige week is overleden aan de gevolgen van Duchenne’s spierdistrofie. Susan vraagt hoe groot de kans is dat haar kind ook duchenne zal krijgen. Haar broer is de enige in de familie die Duchenne heeft. De dragerschapsfrequentie van Duchenne is 1:30. Hoe groot is de kans dat Susan haar kind Duchenne krijgt?
A: 1:12
B: 1:24
C: 1:48
D: 1:60
8. 3 broers hebben een bepaalde aandoening die X-gebonden wordt overerft. De moeder van deze broers heeft dit gen niet. Welke uitspraak is juist:
A: De vader heeft het X-gen met de ziekte.
B: Er is sprake van nonpenetrantie
C: Er is 3x een noveau mutatie opgetreden
9. 3 broers hebben een bepaalde aandoening die X-gebonden wordt overerft. De moeder van deze broers heeft.....read more
Oefenmateriaal bij Gezonde en Zieke Cellen 1 (GZC)Bevat blokspecifiek oefenmateriaal met antwoorden uit voorgaande collegejaren.
A. Threonine
B. Thyrosine
C. Alanine
D. Serine
A. Voor de werking van DNA helicase is ATP hydrolyse nodig.
B. DNA replicatie is onafhankelijk van RNA primers.
C. DNA polymerase bevat endonuclease activiteit (endonuclease activiteit is het vermogen van een enzym DNA in het midden van een keten af te breken).
A. DNA mismatch repair functioneert niet goed in de ziekte HNPCC.
B. DNA schade heeft geen invloed op de celcyclus.
C. Proofreading corrigeert alle fouten gemaakt tijdens DNA replicatie.
A. DNA-mismatch repair
B. Het proces dat cross-links uit DNA haalt
C. Het proces dat breuken in DNA repareert
D. Het proces dat thymine dimeren uit het DNA verwijdert
A. DNA polymerase
B. DNA helicase
C. DNA ligase
D. DNA primase
C. Alanine
Bij het proces van fosforylering van eiwitten wordt een fosfaatgroep covalent gebonden aan een zijgroep van een aminozuur. Dit kan echter slechts bij 3 verschillende aminozuren: Serine, Threonine en Tyrosine, en dus niet bij Alanine.
A. Voor de werking van DNA helicase is ATP hydrolyse nodig.
A: DNA helicase is het eiwit dat betrokken is bij de scheiding van twee DNA strengen. Tijdens dit proces moeten de waterstofbruggen tussen de tegenover elkaar liggende nucleotidebasen worden verbroken. Hiervoor is energie nodig die vrijkomt bij de hydrolyse van ATP.
B: Onjuist. DNA polymerase kan stukjes nucleotiden toe voegen aan het 3’uiteinde van een groeiende polynucleotideketen. Het is echter niet in staat om een nieuwe polynucleotide keten te beginnen. Daarom wordt eerst een stukje complementair RNA op de DNA matrijs neergelegd (RNA primers).
C. Onjuist. DNA polmyerase heeft geen endonuclease activiteit. Wel bevat DNA polymerase exonuclease activiteit. Dit is het vermogen DNA vanaf een uiteinde (en dus niet in het midden van een keten) af te breken. Van dit mechanisme wordt gebruik gemaakt bij proofreading door DNA-polymerase.
A. DNA mismatch repair functioneert niet goed in de ziekte HNPCC.
A. HNPCC (Hereditair Non-Polyposis Colonrectaal Carcinoom) is een erfelijk tumorsyndroom dat wordt veroorzaakt door een afwijking in een gen dat codeert voor een mis-match-repair-eiwit. Doordat deze eiwitten niet goed functioneren, is het zelfherstellend vermogen van het DNA verminderd.
B. Onjuist. DNA schade heeft wel invloed op de celcyclus. Tijdens de checkpoints van de celcyclus wordt onder andere gekeken of DNA beschadigd is, en of wel of niet kan worden doorgegaan met.....read more
Samenvatting bij de colleges bij Gezonde & Zieke Cellen 2 (GZC), week 1Deze samenvatting van de colleges is gebaseerd op het studiejaar 2013-2014.
Alle afbeeldingen in deze samenvatting zijn opgenomen in de bijlage die je hieronder los kunt downloaden.
Normale groei van cellen is goed gecontroleerd. Een voorbeeld van normale groei is na weefselschade, of de turn-over van maagslijmvlies in het maagdarmkanaal. Een andere soort van gecontroleerde groei is aangepaste groei. De ene celsoort gaat over in de andere. Er is sprake van adaptatie. Wanneer de groei niet goed gecontroleerd is, is er sprake van autonome groei. De cellen vermenigvuldigen zich zonder dat zij reageren op de contactremming. Er is dan sprake van tumorgroei.
Groeistoornissen:
Groeistoornissen kunnen worden onderverdeel in gecontroleerde groeistoornissen en ongecontroleerde groeistoornissen. De gecontroleerde groeistoornissen worden weer verder onderverdeeld in:
kwantitatieve groeistoornissen. Binnen deze groei wordt onderscheid gemaakt in:
Hypertrofie: Het orgaan wordt groter, doordat de individuele cellen groter worden. Dit kan een pathologisch of fysiologisch proces zijn. Pathologisch: het groeien van het hart bij hypertensie of klepafwijkingen. Fysiologische hypertrofie: het groeien van de uterus bij zwangerschap en het groeien van de spieren bij bodybuilders.
Hyperplasie: Het orgaan wordt groter doordat de cellen zich delen. Dit kan een pathologisch of fysiologisch proces zijn. Pathhhologisch: prostaatgroei bij oudere mannen. Fysiologisch: lacterende mamma. Er kan ook een combinatie voorkomen van hyperplasie en hypertrofie.
Atrofie: Het orgaan wordt kleiner doordat zowel de grootte als het aantal cellen in het orgaan afneemt. Dit kan optreden als een orgaan nier meer van bloed wordt voorzien, niet meer wordt geïnnerveerd, geen hormonale beïnvloeding meer krijgt of niet meer beweegt.
Hypoplasie: Het orgaan is niet volledig tot ontwikkeling is gekomen. Het orgaan bevat hierdoor minder cellen dan in de normale situatie en is dus kleiner.
Aplasie: Het orgaan is wel aangelegd, maar niet tot ontwikkeling gekomen.
Agenese: Het orgaan is niet aangelegd.
Kwalitatieve groeistoornissen: Binnen deze groep wordt onderscheid gemaakt tussen:
Metaplasie: Een uitgerijpt gedifferentieerd weefsel gaat over in een ander uitgerijpt gedifferenteerd weefsel. Dit kan bijvoorbeeld optreden bij chronische irritatie. Er is dan sprake van een verandering in celtype, die beter bestand is tegen de stress-situatie. Deze verandering is reversibel. Een voorbeeld is de verandering van cilinderepitheel naar plaveiselepitheel in de bronchi bij roken.
Dysplasie: Er is sprake van abnormale rijping, waardoor het weefsel ordeloos wordt. De cellen zien er afwijkend uit. Er verlies van uniformiteit en differentiatie. Er zijn vaak meer celdelingen dan normaal. Er kan
Samenvatting bij de colleges bij Gezonde & Zieke Cellen 2 (GZC), week 2Deze samenvatting van de colleges is gebaseerd op het studiejaar 2013-2014.
Incidentie van longkanker is 11500 per jaar in Nederland en per jaar gaan er ook zo'n 10000 mensen dood aan longkanker. Het is de vierde meest voorkomende vorm van kanker. Het is wel de meest dodelijkste vorm. De verhouding tussen mannen en vrouwen met longkanker is 1.55:1.00. 1 op de 15 mannen krijgt longkanker voor het 75 jaar. Bij vrouwen is dit 1 op de 25.
Het grootste risico voor het krijgen van longkanker is roken. Zo'n 85-90% van de patiënten met longkanker hebben gerookt, of roken. Het risico op longkanker neemt ook al toe door passief roken met 19%. Er gaan in Nederland zo'n 200 mensen dood ten gevolge van passief roken. Inmiddels is het meeroken veel minder.
Roken is dus een risicofactor voor het krijgen van longkanker. Dit wil niet zeggen dat als je nooit gerookt heb, je geen longkanker kan krijgen. Roken verhoogt de kans op longkanker, keelkanker, blaaskanker, hart-en vaatziekten en COPD.
Als je het hebt over preventie, dan heb je het over het vermijden van risicofactoren. Omgevingsfactoren spelen namelijk een grote rol in het ontwikkelen van longkanker. Gedacht wordt dat genetica hierbij ook een rol speelt. Dit is echter nog niet aangetoond. Screening wordt op dit moment nog niet toegepast. Er zou bij screening gebruik kunnen worden gemaakt van een CT-thorax. Een X-thorax en sputum cytologie zijn hiervoor niet geschikt.
Er zijn twee belangrijke soorten longkanker
NSCLC: non small cell lung carcinoma. Het niet-kleincellig longcarcinoom
SCLC: small cell lung carcinoma.
Het is belangrijk om te weten met welke van de twee je te maken hebt voor de behandeling en de prognose.
Als je kijkt naar het niet-kleincellig longcarcinoom onderscheiden we het adenocarcinoom, het plaveiselcelcarcinoom en het grootcellig ongedifferentieerd carcinoom. Ook hier is het onderscheid belangrijk voor de soort therapie, met name binnen de chemotherapie.
In zo'n 20% van de gevallen gaat het om een kleincellig longcarcinoom. De rest is niet-kleincellig.
Symptomen van longkanker zijn over het algemeen zeer aspecifiek. Er kunnen klachten zijn van hoesten, kortademigheid, hemoptoë, thoracale pijn, pneumonie, gewichtsverlies, algehele malaise, koorts en gegeneraliseerde zwakte. De longtumor zelf kan geen pijn veroorzaken, want in het longweefsel zelf zitten geen pijnreceptoren. Wanneer de tumor ingroeit in de pleura kan er.....read more
Oefentoetsen bij Gezonde & Zieke Cellen 2 (GZC)Drie oefentoetsen, gebaseerd op 2007, 2008 & 2009. Let op: alleen de oefentoets van 2009 heeft antwoorden.
Algemene oncologie
1. Een voorbeeld van een tumor die overwegend hematogeen metastaseert is het:
a. mammacarcinoom
b. ovariumcarcinoom
c. niercelcarcinoom
2. Longmetastasen van een schildkliercarcinoom zijn een voorbeeld van metastasering via de:
a. vena pulmonalis
b. vena cava
c. vena porta
3. Het ontstaan van een urotheelcelcarcinoom van de blaas, is geassocieerd met
a. roken
b. Schistosoma infectie
c. asbest contact
4. Welke van de volgende micro-organismen kan gezien worden als een biologische verwekker van kanker?
a. Epstein-Barr-virus
b. Cytomegalie virus
c. Hepatitis A virus
5. Tot de meest frequente vormen van kanker bij kinderen horen:
a. melanomen
b. hersentumoren
c. longtumoren
6. Bij het typische incidentie-patroon van een West-Europees land , hoort een relatief lage incidentie van:
a. coloncarcinoom
b. cervixcarcinoom
c. longcarcinoom
Mamma
7. Alvorens tot een operatieve behandeling over te gaan, wordt bij de verdenking op mammacarcinoom eerst de zgn. “triple diagnostiek” verricht. Dit houdt in:
a. lichamelijk onderzoek, mammografie en echografie
b. mammografie, echografie en weefseldiagnostiek (cytologie en/of histologie)
c. lichamelijk onderzoek, mammografie/echografie en weefseldiagnostiek
8. Welke zenuwen komt u allemaal tegen in de oksel bij een okselklierdissectie? Geef het beste antwoord.
a. nn intercostobrachialis en n thoracicus longus
b. n axillaris, n brachialis en n thoracodorsalis
c. nn intercostobrachialis, n thoracicus longus en n thoracodorsalis
9. Bij een multifocaal mammacarcinoom, zonder doorgroei of infiltratie van de huid is
a. een gemodificeerde radicale mastectomie geïndiceerd
b. ablatio van de mamma in combinatie met een schildwachtklier procedure een goede behandeling
c. een mammasparende behandeling mogelijk
10. Er bestaan verschillende soorten mammacarcinomen. Welke komt verreweg het meeste voor?
a. invasief lobulair mammacarcinoom
b. slijmvormend adenocarcinoom
c. invasief ductaal carcinoom
11. Patiënte ondergaat een ablatio mammae wegens DCIS graad III. Dit is radicaal verwijderd. Welke nabehandeling zal nu volgen?
a. radiotherapie
b. hormoontherapie
c. geen
12. Patiënt ondergaat een segment excisie van de mamma wegens DCIS graad I. Dit is niet radicaal verwijderd. Welke nabehandeling zal nu volgen?
a. radiotherapie
b. re-excisie
c. hormoontherapie
Longziekten
13. Mediastinoscopie is belangrijk voor:
a. het vaststellen van de aard van de tumor (kleincellig of niet-kleincellig)
b. stadiering van een longcarcinoom
c. diagnostiek van perifeer gelegen longtumoren
14. Een patiënt met een longcarcinoom heeft een verhoogd alkalische fosfatase en hypercalciemie. In dit geval is het verstandig het standaard disseminatie onderzoek uit te breiden met:
a. een echografie of CT-scan van de bovenbuik
b. een CT-scan van de hersenen
c. een botscintigrafie
15. Een kleincellig longcarcinoom wordt in principe behandeld met:
a. chemotherapie
b. chirurgie
c. radiotherapie
16. Als co-morbiditeit bij patiënten met.....read more
Begrippen bij Gezonde & Zieke Cellen 2 (GZC)Bulletpoint samenvatting voor het vak GZC II met alle belangrijke begrippen met toelichting. Gebaseerd op 2014-2015.
Bulletpoint samenvatting
Algemeen | |
| nieuwvorming |
| abnormale massa waarvan groei die van normale weefsels overstijgt, ongecoördineerd is en doorgaat nadat de stimulus is gestaakt |
| een afwijking, die histologisch de normale componenten toont van het orgaan waarin de afwijking gelokaliseerd is, maar in een abnormale rangschikking en graad van differentiatie bron: Ned Tijdschr Geneeskd. 1990;134:481-3 naar Albrechts, die de term hamartoom voor het eerst omschreef |
| normaal weefsel op de verkeerde locatie |
| toegenomen variatie in kern (vorm, grootte, etc..) |
| kernen zijn donkerder door toegenomen hoeveelheid DNA |
| verhouding van kerngrootte ten opzichte van de hoeveelheid cytoplasma |
| oriëntatie van de kernen in het cytoplasma |
| reversibele verandering van een celtype wordt verwisseld voor een ander als reactie op een prikkel; verandert terug als je de prikkel “weghaalt”; wanneer metaplasie sneller plaatsvindt of zonder prikkel kan dit een predispositie voor maligniteit zijn |
| toename van het aantal cellen |
| metaplasie met polymorfie, toegenomen aantal nucleoli, meer mitose, verlies van eigenschappen, verlies van architectuur |
| in hoeverre zie je nog het originele weefsel: goed, matig (tumor zichtbaar, maar je ziet van welk weefsel), slecht (te veel tumor om te zien van welk weefsel het afkomstig is), anaplasie/ongedifferentieerd |
| benigne is niet invasief, niet destructief, metastaseert niet; krijgt uitgang –oom; benigne tumoren kunnen wel klinisch relevant zijn als ze andere weefsels verdrukken (kan het geval zijn bij een meningioom) |
| tumor van slijmvliezen |
| vleesboom |
| invasief, destructief, lymfogene en/of hematogene metastasering; krijgen de naam –sarcoom of –carcinoom; uitzonderingen: lymfoom, mesothelioom en melanoom (zijn maligne!) |
| als tumorcellen in het “doelwitorgaan” een nieuwe tumor hebben gevormd spreekt men van metastase, route die wordt gevolgd:
bron: introductiecollege GZC II |
Gezonde & Zieke Cellen 2 (GZC 2) - B2 - Geneeskunde - UU - OefententamensBevat leeropdrachten bij Gezonde & Zieke Cellen 2 (GZC 2), gebaseerd op 2015-2016
Aanvankelijk is er sprake van een carcinoma in situ, die kan overgaan in een maligne vorm. Wanneer dit gebeurt, is niet bekend. Borstkanker heeft veelal een lage groeifractie (cellen in celcyclus) met een verdubbelingstijd van gemiddeld ruim 200 dagen. Tumoren van 1-2 cm noemen we klinisch vroeg ontdekte carcinomen, hoewel de tumor biologisch dan al ten minste twee derde van zijn totale groei heeft ondergaan en er derhalve eerder van een late ontdekking sprake is. Lokale infiltrerende groei is het gevolg van de vermeerdering van tumorcellen in het borstklierweefsel, waarin neoplastische groei is ontstaan. De meeste tumoren worden gevonden in het laterale bovenkwadrant, waar zich het meeste mammaweefsel bevindt. Bij microscopisch onderzoek worden echter meer, veelal niet-infiltrerende, onafhankelijke carcinomen gevonden. Infiltrerende ingroei vindt plaats langs de klierbuisjes, de bindweefselstrengen en het weinig weerstand biedende vetweefsel in de borst. Tumorcellen kunnen lymfevaten en bloedvaten op dezelfde wijze als witte bloed lichaampjes penetreren. Op deze wijze kan al voor de tumor ontdekt is metastasering plaatsvinden (Van der Velde, 7e druk, 2005).
Steeds meer gegevens tonen aan dat behandeling in een vroege fase en het bereiken van een plaatselijke genezing van invloed zijn op de uiteindelijke genezingskans.
Chirurgie.
Er zijn twee mogelijkheden: de mammasparende operatie en de gemodificeerde radicale mastectomie. Welke het wordt, hangt af van tumorgrootte, calcificaties, het te verwachten cosmetische resultaat en de wens van de patiënt. Multicentriciteit en macroscopische irradicaliteit zijn contra-indicaties voor MST (mamma-sparende therapie). De radicale mastectomie bestaat uit een ablatio mammae inclusief een okselklierdissectie. Bij het okselkliertoilet worden de n. thoracodorsalis en de n. thoracicus longus zo mogelijk gespaard. De schildwachtklierprocedure is een geaccepteerd alternatief voor de okseldissectie. De beste resultaten worden bereikt met een combinatie van preoperatieve lymfoscintigrafie met radiocolloïd en preoperatieve injectie met patentblauw. Contra-indicaties zijn multipele tumorhaarden, tumor groter dan T2 en klinisch verdachte okselklieren. Bij een positieve schildwachtklier dient okselklierdissectie/okselkliertoilet te volgen.
Radiotherapie.
Reduceert het.....read more
Gezonde & Zieke Cellen 2 (GZC 2) - B2 - Geneeskunde - UU - Notes (1415)Bevat aantekeningen bij de colleges, werkgroepen etc. gebaseerd op het studiejaar 2014-2015
Er zijn twee soorten gecontroleerde groei van cellen: normale groei (bijvoorbeeld herstel na weefselschade of turnover van maagslijmvlies) en adaptatie. Wanneer groei ongecontroleerd is, is er sprake van autonome groei ofwel tumorgroei: cellen delen onafhankelijk van signalen uit hun milieu.
Groeistoornissen
Groeistoornissen kunnen worden onderverdeel in gecontroleerde groeistoornissen en ongecontroleerde groeistoornissen. De gecontroleerde groeistoornissen worden weer verder onderverdeeld in:
Kwantitatieve groeistoornissen.
Hypertrofie: cellen worden groter. Dit kan een pathologisch of fysiologisch proces zijn. Pathologisch: het groeien van het hart bij hypertensie of klepafwijkingen. Fysiologisch: het groeien van de uterus bij zwangerschap en het groeien van de spieren bij bodybuilders.
Hyperplasie: cellen vermeerderen zich. Dit kan een pathologisch of fysiologisch proces zijn. Pathologisch: prostaatgroei bij oudere mannen. Fysiologisch: lacterende mammaklieren. Er kan ook een combinatie voorkomen van hyperplasie en hypertrofie.
Atrofie: grootte en aantal cellen neemt af. Dit kan optreden als een orgaan niet meer van bloed wordt voorzien, niet meer wordt geïnnerveerd, geen hormonale beïnvloeding meer krijgt of niet meer beweegt.
Hypoplasie: er zijn weinig cellen. Een orgaan is dan niet volledig tot ontwikkeling is gekomen en kleiner van omvang.
Aplasie: er zijn geen cellen. Het orgaan is wel aangelegd, maar niet tot ontwikkeling gekomen.
Agenese: het orgaan is niet aangelegd.
Kwalitatieve groeistoornissen:
Metaplasie: een compensatiemechanisme
Essential Cell Biology (Alberts et al) - KernbegrippenBevat de belangrijkste begrippen uit het boek Essential Cell Biology met uitleg
Terminologie
Regionale anatomie Lichaam verdeeld in delen als romp en hoofd.
Systemische anatomie Lichaam verdeeld in orgaansystemen die samenwerken.
Klinische anatomie Manier waarop lichaam gebruikt wordt in geneeskunde.
Mediane vlak Vlak verticaal door midden van lichaam.
Sagittale vlak Vlak verticaal parallel aan mediane vlak.
Frontale vlak Vlak verticaal loodrecht op mediane vlak.
Transversale vlak Vlak horizontaal door het lichaam.
Superior/Craniaal Dichterbij het hoofd.
Inferior/Caudaal Dichterbij de voeten.
Anterior/Ventraal Dichterbij de voorkant (buik).
Posterior/Dorsaal Dichterbij de achterkant (rug).
Mediaal In het midden/centrum van het lichaam.
Lateraal Naar de zijkanten van het lichaam.
Proximaal Dichterbij een bepaald punt (meestal hoofd).
Distaal Verder van een bepaald punt af (meestal het hoofd).
Unilateraal Aan één zijde.
Bilateraal Aan beide zijde.
Ipsilateraal Aan dezelfde zijde.
Contralateraal Aan de andere zijde.
Flexie Buiging van een bepaald lichaamsdeel.
Extensie Strekken van een bepaald lichaamsdeel.
Huid
Epidermis Buitenste laag van de huid bestaande uit bovenste keratinelaag en daaronder gelegen basale laag.
Dermis Middelste laag bestaande uit collageen, elastische vezels en bevat follikels, zenuwen,bloedvaten talg- en haarklieren.
Subcutaan vetweefsel Onderste laag bestaande uit vet en los bindweefse
Functie van de huid Bescherming, warmteregulatie, gevoel en synthese van vitamine D
Skelet
Axiale skelet Botten van hoofd, nek en romp.
Appendiculaire skelet Botten van ledematen.
Kraakbeen Bevindt zich op gewrichten en flexibele delen.
Perichondrium Vlies om kraakbeen voor voeding, groei van nieuw
kraakbeen en aanhechting van pezen en ligamenten.
Bot, functie Bescherming, beweging, opslag van zouten en bloedcelnieuwvorming.
Periostium Vlies om bot met dezelfde functies als perichondrium.
Compact bot Oppervlakkige laag van het bot.
Diafyse Middelste plaat van het bot.
Epifyse Platen aan beide uiteinden van het bot.
Epifysiale platen De plek waar het bot groeit richting diafyse.
Voedingsarteriën Voorzien het spongieuze bot en beenmerg van bloed.
Periostale arteriën Voorzien het compacte bot (van diafyse).
Epifysiale arteriën Voorzien de uiteindes (epifysen) van het bot.
Sensorische zenuwen Zitten voornamelijk in het periostium.
Vasomotorishe zenuwen Zitten in het bot om diameter van bloedvaten te regelen.
Gewrichten
Gewrichten Op plaatsen waar twee structuren elkaar raken.
Fibreuze gewrichten Zitten aan elkaar vast door fibreus bindweefsel.
Synoviaal gewrichten Synoviale vloeistof tussen gewrichtsoppervlakken voor voeding en een glad glijdoppervlak.
Articulaire arteriën en venen Arteriën en venen die zich in het gewrichtskapsel bevinden.
Spieren
Skeletspierweefsel Vrijwillige beweging, bestaat uit spierweefsel en pees.
Hartspierweefsel Spierweefsel in hart, niet beïnvloedbaar door eigen wil.
Glad spierweefsel In wanden van bloedvaten, organen, haarzakjes, lens en pupil.
Lange spieren Worden het kortst als ze samentrekken, niet sterk.
Korte spieren Worden niet zo kort, maar wel sterk.
Oorsprong Het deel van de spier dat op een.....read more
Summary: Essential Cell Biology (Alberts et al) - First partThis summary is based on the 3rd edition of Essential Cell Biology from Alberts et al. The remaining chapters can be accessed when logged in and can be found here: Second part of the summary
Cells are the fundamental units of life; all living things are made of cells. The present-day cells are believed to have evolved from an ancestral cell that excited more than 3 billion years age. Cells vary enormous in appearance and function, however all living cells have a similar basic chemistry.
With the invention of the microscope, it became clear that plants and animals are assemblies of cells, that cells can also exist as independent organisms, and that cells individually are living in the sense that they can grow, reproduce, convert energy from one form into another, respond to their environment, and so on. Although cells are varied when viewed from the outside, all living things are fundamentally similar inside. And in all living things, genetic instructions, called genes, are stored in DNA molecules. In every cell, the instructions in the DNA are read out, or transcribed, into a chemically related set of molecules made of RNA. The messages carried by the RNA molecules are in turn translated into yet another chemical form: they are used to direct the synthesis of a huge variety of large protein molecules that dominate the behaviour of the cell. In sum, the reproduction process exists of replication (DNA synthesis), transcription (RNA synthesis) and translation (protein synthesis). Unfortunately, the copying of DNA is not always perfect, and the instructions are occasionally corrupted. Later is this summary we will discuss this further.
Cells are enclosed by a plasma membrane that separates the inside of the cell from the environment. And all cells contain DNA as a store of genetic information and use it to guide the synthesis of proteins. Cells in a multicellular organism, though the all contain the same DNA, can be very different. They use their genetic information to direct their biochemical activities according to cues they receive from their environment.
Cells of animal and plant tissues are typically 5-20 micrometer in diameter and can be seen with a light microscope, which also reveals some of their internal components (organelles). The electron microscope permits the smaller organelles and even individual molecules to be seen, but specimens require elaborate preparation and cannot be viewed alive. So, the invention of the light microscope led to.....read more
Summary: Essential Cell Biology (Alberts et al) - Second partThis summary is based on the 3rd edition of Essential Cell Biology from Alberts et al. The first 10 chapters are open access and can be found here: First part of the summary
Cell membranes enable a cell to create barriers that confine particular molecules to specific compartments. The simplest bacteria have only a single membrane, the plasma membrane. Eucaryotic cells, however, contain in addition a profusion of internal membranes that enclose intracellular compartments. All cell membranes are composed of lipids and proteins and share a common general structure. The lipid component consists of many millions of lipid molecules forming a lipid bilayer. This lipid bilayer gives the membrane its basic structure and serves as a permeability barrier.
The lipids in cell membranes combine two very different properties in a single molecule: each lipid has a hydrophilic (‘water-loving’) has and one or two hydrophobic (‘water-hating’) hydrocarbon tails. There are three major classes of membrane lipid molecules:
The most abundant lipids in cell membranes are phospholipids, and the most common type of phosphoslipid in most cell membranes is phosphatidylcholine. Molecules with both hydrophilic and hydrophobic properties are termed amphipathic. This chemical property plays a crucial part in driving these lipid molecules to assemble into bilayers. They assemble spontaneously into bilayers when placed in water, forming closed compartments that reseals of torn.
Amphipathic molecules re subject to two conflicting forces: the hydrophilic head is attracted to water, while the hydrophobic tail shuns water and seeks to aggregate with other hydrophobic molecules. This conflict is resolved by the formation of a lipid bilayer, because the hydrophilic heads face the water at each of the two surfaces of the sheet of molecules and the hydrophobic tails are all shielded from the water and lie next to one another in the interior of this ‘sandwich’. Finally, the phospholipid bilayers spontaneously close in on themselves to form sealed compartments.
The lipid bilayer is fluid, and individual lipid molecules are able to diffuse within their own monolayer; they do not, however, spontaneously flip from one monolayer to the other. The two layers of the lipid bilayer have different lipid compositions, reflecting the different functions of the two faces of a cell membrane.
The fluidity of a cell membrane (the ease with which its lipid molecules move within the plane of the bilayer) is important for membrane function and has to be
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Cell biology Vinayak rajesh patil contributed on 14-11-2019 13:25
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