cellular bio Flashcards
(93 cards)
1
Q
What are common features between prokaryotic and eukaryotic cells ?
A
the plasma membrane has similar construction; the genetic information is encoded in dna, similar transcription and translation, shared methabolic pathways
2
Q
what are the two types of prokaryotic cells ?
A
archaea: includes several groups of organisms with similar nucleotide sequences
bacteria: they’re present in every habitat. the most complex are cyanobacteria, which contain elaborate errays of cytoplasmic membranes. many cyanobacteria are capable of nitrogen fixation.
3
Q
what are viruses ?
A
obligateintraccellular parasites: they cannot reproduce unless present in a host cell. outside of a cell, the virus exists as a virion: the virion contains a small amount of genetic material surrounded by a capsid.
4
Q
what are the two types of viral infection ?
A
the basic one is the litic cycle: the virus arrests the normal synthetic activities of the host and redirects the cell to use its materials to create viral proteins and nucleic acids. the infected cell ruptures and releases a new generation of viral particles.
lysogenic: the virus integrates its DNA into the DNA of the host cell’s chromosomes. the integrated viral DNA is called a provirus.
4
Q
adenoviruses and retroviruses
A
adenoviruses: commonly acquired by contact with secretions.
retroviruses: their replicative strategy includes reverse trancritpion of the virion RNA into linear double-stranded DNA and the subsequent integration of this DNA into the genome of the cell. they’re divided into simple and complex, and distinguishable by the organization of their genomes. all retroviruses contain three coding domains: gag (directs synthesis of proteins that form the matrix, capsis and nucleoprotin structures), pol (contains info for reverse transcriptase and integrase enzymes) and env (surface and transmembrane components). they carry also pro, which encodes the virion protease.
4
Q
the 7 plasma membrane functions
A
1>compartmentalization (it encloses the contents of the entire cell, allowing specialized activities to proceed without external interference and independency)
2>scaffold for biochemical activities
3>providing a semipermeable barrier (prevent the unrestricted exchange of molecules and provide the means of communications between compartments)
4>transporting solutes (machinery for physically transporting substances from one side to the other, from a region with higher concentration to one with lower concentration; it allows the cell to accumulate substances.
5>responding to external stimuli (signal tranduction: membranes posses receptors that combine with specific molecules called ligans or respond to other types of stimuli such as light or mechanical tension)
6>intercellular interaction (situated at the outher edge of the cell, it mediates the interactions between a cell and its neighbors)
7>energy transduction (membranes are involved in the processes in which one tupe of energy is converted into another one)
4
Q
phosphoglycerides
A
most membrane lipids contain a phosphate group, which makes them phospholipids. membane glycerids are diglycerides (only two of the hydroxyl groups of the glycerol are esterified to fatty acids). membrane phosphoglycerides instead have an additional groups linked to the phosphate (choline, serine or inositol). each of these groups is small and hydrophilic, forming a highly water soluble domain at one end of the molecule, called head group.
5
Q
sphingolipids
A
they’re derivates of sphingosine, an amino alcohol that contains a long hydrocarbon chain. sphingosine is linked ot a fatty acid by its amino groups: ceramide. they are also amphipathic.
6
Q
cholesterol
A
these molecules are oriented with their small hydrophilic hydroxyl group toward the membrane surface and the remainder of the molecule embedded n the lipid nilaryer. the hydrophobic rings are glat and rigid, and interfere with the movements of the fattu acid tails of the phospholipids.
7
Q
lipid bilayer
A
The lipid bilayer is thought to facilitate the regulated fusion or budding of membranes. Another important feature of the lipid bilayer is its ability to self‐assemble. The lipid bilayer consists of two distinct leaflets that have a distinctly different lipid composition.
8
Q
membrane cargohydrates
A
more than 90 percent of the membrane’s carbohydrate is covalently linked to proteins to form glycoproteins; the remaining carbohydrate is covalently linked to lipids to form glycolipids.
9
Q
membrane proteins
A
each protein has a defined orientation relative to the cytoplasm, so that the properties of one side of the membrane are different from the ones of the other side (sidedness).
10
Q
integral proteins
A
they penetrate the lipid bilayer. they are transmembrane proteins: they pass entirely through the lipi bilayer and have domains that protrude from both the extracellular and cutoplasmic sides of the membrane. some integral proteins have only one membrane spanning segment whereas others are multispanning. they mostly function as receptors that bind specific substances at the membrane surface or as agents that transfer electrons during photosynthesis and respiration. they are also amphipatic.
11
Q
peripheral proteins
A
located entirely outside the lipid bilayer, on either side. they are associated to the membrane by noncovalent bonds. the ones on the inside form a fibrillar network that act as a membrane skeleton. these proteins provide mechanical support for the memrbane and function as an anchor for integral membrane proteins. others function as enzymes, coeats or factors that transmit transmembrane signals. they typically have a dynamic relationship with the membrane.
12
Q
lipid-anchored proteins
A
located outside the lipid bilayer, on either the extracellular or cytoplasmic surface, covalently linked to a lipid molecule that is situated within the bilayer. numerous proteins present on the external surface are linked to a phosphatidylinositol that is embedded in the outher leaflet.
13
Q
membrane fluidity
A
at 37° C the layer is described as a liquid crystal: the molecules retain a specific orientation. if the temperature is lowered, a point is reached in which the layer changes. the lipid is convertent from a liquid to a frozen crystalline gel in which the movement of the phospholipid fatty acid chains is greatly restricted. the temperature at which this happens is called the transition temperature. membrane fluidity provides a perfect compromise between a rigid and ordered structure (mobiliyy absent) and a completely fluid liquid (the components of the membrane could not be oriented and structural organization and mechanical support would be lacking). most of the basic cellular processes depend on the movement of membrane components and would probably not be possible if membranes were rigid.
14
Q
maintenance of membrane fluidity is an example of homeostasis.
A
remodeling of the cell is started by enzymes that remodel membranes by desaturating single bonds (desaturase) in fatty acyl chains to form double bonds and reshuffling (phospholipases) the chains between different phospholipid molecules to produce ones that contain two unsaturated fatty acids.
15
Q
solute movement across cell membranes
A
membranes are said to be semipermeable because water passes more rapidly through them than do dissolved ions or small polar organic solutes. water moves from a region of lower solute concentration to a region of higher solute concentration. when these two compartments are separated by a semipermeable membrane, the compartment with a higher concentration is said to be hypertonic, while the one with the lower concentration is hypotonic. once the two concentrations are equal, both fluids are isotonic.
16
Q
diffusion of ions
A
1 > voltage gated channels: their conformational state depends on the difference in ionic charge on the two sides of the membrane
2 > ligand gated channels: their conformational state depends on the binding of a specific molecule (the ligand), which is usually not the solute that passes through the channel. some ligand gated channels are opened or closed following the binding of a molecule to the outer surface of the channel, others are opened or closed following the binding of a ligand to the inner surface of the channel
3 > mechano gated channels whose conformational state depends on mechanical forces that are applied to the membrane
17
Q
facilitated diffusion
A
the diffusing substance first binds selectively to a membrane-spanning protein (facilitative transporter) that facilitates the diffusion process. the binding triggers a conformational change in the protein, exposinh the solute to the other surface of the membrane, from where it can diffuse down its concentration gradient.
18
Q
active transport
A
depends on integral proteins. unlike facilitated diffusion, however movement of a solute against a gradient reuired the coupled input of energy. the endoergonic movement of ions or other solutes across the membrane against a concentration gradient is coupled to an exergonic process. proteins that carry out active transport are often referred to as pumps. active transport drives the movement of ions in only one direction.
19
Q
Na/K pump
A
the pump has higher affinity for sodium ions than potassium ions, thus after binding ATP it binds 3 cellular Na ions. ATP is hydrolyzed, leading to phosphorylation of the pump at a highly conserved aspartase residue and subsequent release of ADP. this process leads to a conformational change in the pump. this change exposes the Na ions to the extracellular region. the phosphorylated form of the pump has a low affinity for Na ions so they are released; by contrast it has high affinity for the K ions. the pump binds 2 extrecellular K ions, which induces dephosphorylation of the pump, reverting it to its previous conformational state, thus releasing K ions into the cell. the unphosphorylated form of the pump has a higher affinity for Na, so ATP binds and the process starts again.
20
Q
types of pumps
A
P-type: the P stands for phosphorylation, indicating that during the pumping cyvle the hydrolysis of ATP leads to the transfer of the released phosphate group to an aspartic acid residue of the transport protein
F-ATPase: mitochondrial and chloroplast ATP synthase
V.ATPase: vacuolar ATPase
ABC (ATP vinding cassette) transporter
21
Q
resting potentials
A
the presence of a membrane potential is not unique to nerve cells; such potentials are present in all types of cells. whe a nerve or muscle cell in in an unexcited state, the membrane potential is referred to as the resting potential (-70 mV) because it is subject to dramatic change.
22
the action potential
if the stimulus causes the membrane to depolarize by only a few millivolts, the membrane rapidly returns to its resting potential as soon as the stimulus has ceased. if the stimulus depolarizes the membrane beyond a certain point (threshold > -50mV), the change in voltage causes the voltage gated sodium channels to open. sodium ions diffuse freely into the cell down both their concentration and electric gradients. the increased permeability of the membrane to Na ions and the corresponding movement of positive charge into the cell causes the membrane to reverse potential, becoming positive (+40 mV). the sodium channels inactivate blocking influx of Na ions. the change in membrane potential triggers the potassium channels. as a result, potassium diffuses freely. the decreased permeability of the membrane to Na and increased to K causes the membrane potential to swing back to -80 mV. the potassium channels close. following an action potential, the membrane enters a refractory period: it cannot be restimulated. once the membrane is depolarized, a full blown action potential is triggered without further stimulation. this feature is known as the all-or-none law.
23
action potential as an impulse
action potential does not remain localized at a particular site but is propagated as a nerve impulse down the lenght of the cell to the nerve terminals. positive ions move toward the site of depolarization. this local flow causes the membrane in the region just ahead of the ction potential to become depolarized. because all impulses traveling along a neuron exhibit the same strenght, stronger stimuli cannot produce bigger impulses than weaker stimuli. the ability to make sensory discriminations depends on several factors. stimulus strenght is also encoded in the pattern and frequency by which action potentials are launched down a particular neuron. in most cases, the stronger the stimulus, the greater the number of impulses generated. the only sites where action potentials can be generated are the nodes of ranvier. an action potential at one node triggers an action potential at the next node, causing the impulse to jump from node to node (saltatory conduction)
24
neurotransmission
a presynaptic cell conducts impulses toward a sunapse and a postsynaptic cell always lies on the receiving side of a synapse. when an impulse reached a terminal knob, the accompanying depolarization induces the opening of a number of voltage-gated Ca channels. Ca ions are normally present at very low concentration and when the gates open, they diffuse into the knob. the elevated calcium triggers the rapid fusion of a sew synaptic vesicles with the membrane, causing the release of neurotransmitter molecules into the synaptic cleft. once released, these molecules diffuse across the narrwo gap and bind selectively to receptor molecules that are concentrated directly across the cleft in the postsynaptic plasma membrane. two effects based on the receptor: 1) the transmitter can trigger the opening of cation-selective channels, leading to an influx of sodium ions and a less negative membrane potential. this depolarization excites the cell, making it more likely to respond to stimuli. 2) the transmitter can trigger the opening of anion-selective channels, leading to an influx of chloride ions and a hyperpolarized membrane potential > less likely the cell will generate action potential
25
synaptic plasticity
synapses are key determinants in the routing of impulses. they act like gates stationed along the various pathways, allowing some pieces of information to pass from one neuron to another, while holding back other pieces or rerouting them in another direction. they can also display plasticity, which is important during infancy and childhood, when the neuronal circuitry achieves its mature configuration.
26
mitochondria
the outer boundary of a mitochondrion contains two membranes: the outer membrane completely encloses the mitochondrion, while the inner membrane is subdivided into two major domains that have different protein residents and carry out distinct functions. one of these domains, the inner boundary membrane, lies inside forming a double-membrane envelove; this envelope is rich in proteins responsible for the import of mitochondrial proteins. the other domain is present within the interior of the organelle as a series of invaginated membranous sheets, called cristae.
the role of mitochondria as energy transducers is intimately tied to the membranes of the cristae: they contain a large amount of machinery needed for aerobic respiration adn ATP formation. the membranes divide the organelle into two aqueous compartments, one within the interior of the mitochondrion (matrix) and a second between the outer and inner membrane, called the intermembrane space. the matrix has a gel-like consistency owing to the presence of a high concentration of water soluble proteins. the matrix also contains ribosomes and several molecules of DNA. this non-chromosomal DNA is important because it encodes a small number of mitochondrial polypeptides tightly integrated into the inner mitochondrial membrane along with polypeptides encoded by genes residing within the nucleus.
27
metabolism
the two products of glycolysis (pyruvate and NADH) can be metabolized in two very different ways, depending on the type of cell in which they are formed and the presence or absence of oxygen. in the presence of oxygen, aerobic organisms are able to extract large amounts of additional energy from the pyruvate and NADH produced during glycolysis.
28
tricarboxylic acid (TCA) cycle
once formed (pyruvate + HS - CoA + NAD -> acetyl CoA + CO + NADH + H), acetyl CoA is fed into a cyclic pathway, where the substrate is oxidized and its energy conserved. the acetyl groups binds to the oxylacetic acid (4C) giving citric acid.
29
the TCA cycle net equation
Acetyl CoA + 2H2O + FAD + 3NAD+ GDP + Pi -> 2CO2+ 3NADH + FADH2 + 3H+ GTP + HS-CoA
30
electron transport chain
protein complexes transfer electrons from electron donors to electron acceptors via redox reaction and couple this transfer with the transfer of protons (H ions) across a membrane. many of the enzymes in the electron transport chain are membrane-bound. the flow of electrons through the electron transport chain is an exergonic process.
31
types of electron carriers
flavoproteins (consist of a polypeptide bound tightly to one of two related prosthetic groups, either flavin adenine dinucleotide, FAD, or flavin kononucleotide, FMN), cytochromes (contain heme prosthetic groups; three distinct types, a b and c), copper atoms (accept and donate a single electron), ubiquinone (UQ/coenzyme Q, lipid-soluble molecule containing a long hydrophobic chain composed of five carbon isoprenoid units; able to accept and donate two electrons and two protons), iron-sulfur proteins (iron is linked to inordganic sulfide ions; the entire complex is capable of accepting and donating only a single electron; electrons are passed from one carrier to the next, losing energy)
32
electron-transport complexes
I > NADH dehydrogenase (the gateway to the electrons transport chain, catalyzing the transfer of a pair of electrons from NADH to UQ to UQH2)
II > succinate dehydrogenase (four polypeptides: two hydrophobic subunits that anchor the protein in the membrane and two hydrophilic subunits that compire the TCAc enzyme)
III > cytochrome BC (catalyzes the transfer of electrons from UQ to cytochrome c. four protons are translocated across the membrane for every pair of electron transferred: they are released into the intermembrane space int wo separate steps powered by the enrgy released as a pair of electrons are separated from one another and passed along; two protons are derived and two additional one are removed from the matrix and translocated across the membrane as part of a second molecule of UQ)
IV > cytochrome oxidase (electrons from reduced cytchrome x to oxygen)
33
lysosomes and peroxisomes
lysosomes: membrane enclosed organelles that contain an array of enzymes capable of breaking down all types of biological polymers; they function as the digestive system of the cell, seving both to degrade material and to digest obsolete components of the cell itself
peroxisomes: multifunctional organelles containing more than 50 enzymes involved in such diverse activities as the oxidation of very long chain fatty acids and the synthesis of plasmalogens (phospholipids in which one of the fatty acids is linked to glycerol by an ether linkage rather than as ester linkage.
34
smooth endoplasmic reticulum
it synthesizes steroid hormones in the endocrine cells of the gonal and adrenal cortex, detoxification in the liver with barbiturates and ethanol and sequestres calcium ions within the cytoplasm of cells
35
rough endoplasmic reticulum
it has 1/3 of the proteins encoded by the genome on its cytosolic surface. these include 1) secreted proteins, 2) integral membrane proteins, 3) soluble proteins that reside within compartments of the endomembrane system. as it enters the RER, a nascend polypeptide is acted on by a variety of enzymes located within either the membrane or the lumen of the RER. the N-terminal is removed by the signal peptidase. the lumen of the ER cisternae provides a specialized local environment that favors the modification, folding and assembly of a selected subset of the cell's proteins. the segregation of these newly synthesized proteins in the cisternae removed them from the cytosol and allows them to be modificed and dispatched toward their ultimate destination.
36
membrane biosynthesis
membranes do not arise ex novo but grow as newly synthesized proteins. most membrane lipid are synthesized entirely withing the endoplasmic reticulum. the enzymes involved in the synthesis of phospholipids are themselves integral proteins of the ER membrane with their active sites facing the cytosol. the membranes of different organelles have different lipid composition (changes take place). most membranous organelles contain enzymes that modify lipids; when vesicles bud from a compartments, some types of phospholipids may be preferentially included within the menbrane of the forming vesicle; cells contain lipid-transfer proteins that can bind and transport lipids through the acqueous cytosol.
37
glycosylation
the addition of sugars to an oligosaccharide is catalyzed by glycosyltransferases. the sequence in which sugars are transferred during assembly of an olifosaccharide depends on the sequence of action of glycosyltransferases in the process. the basal segment of each chain is put together independently on a lipid carrier and then transferred, as a block, to specific asparagine residues of the polypeptide. this lipid carrier, dolichol phosphate, is embedded in the ER. this part begins with the transfer of N-acetylglucosamine1-phosphate, followed by the transfer of another N-acetylglucosamine, then nine mannose and three glucose units. this block is then transferred to asparagines.
38
ribosomes
each ribosome is composed of two subunits, a larger one and a smaller one, typically referred to in terms of their sedimentation rate. they're the istes at which information carries in the genetic cose is converted into protein molecules. ribosomal mRNA determines the order of the tRNA molecules, which determines the amino acid sequence. rRNA catalyzes the peptidyl transferase reaction.
39
the golgi complex
flattened, disklike, membranous cisternae with dilated rims and associated vesicles and tubules. it's divided into several funtionally distinct compartments arranged along an axis from the cis or entry face closest to the ER to the trans or exit face at the opposite end of the stack. the CGN (cis golgi network) works as a sorting station that distinguishes between proteins to be shipped back to the ER and those allowed to procees. the bulk consists of a series of large, flattened cisternae divided into cis, medial and trans. the TGN (trans golgi network) is a sorting staion where proteins are segregated into different types of vesicles heading either to the plasma membrane or to various intracellular destinations. the membranous elements of the golgi complex are thought to be supported mechanically by a peripheral membrane skeleton or scafforl composed of a variety of proteins. the golgi scaffold may be physically linked with motor proteins that direct the movement of vesicles and tubules entering and exiting the golgi complex.
40
vesicle transport
materials are carried between compartments by vesicles that bud from donor membranes and fuse with acceptor membranes. most of the vesicles are covered by an electron-dense layer, a protein coat formed by soluble proteins. protein coats have two distinct functions: 1) they act as a mechanical devide that causes the membrane to curve and form a budding vesicle; 2) they provide a mechanism for selecting the components to be carried . several distinct classes of coated vesicles have been identified, the most important three are: 1) COPII-coated vesicles that move materials from the ER to the ERGIC (ER-Golgi Intermediate Compartment) and GC (they select and concentrate certain components for transport in vesicles); 2) COPI-coated vesicles that move from the ERGIC and GC to the ER and from the TGN to the CGN; 3) clathrin-coated vesicles that move materials from the TGN to endosomes, lysosomes.
41
exocytosis
the fusion of a secretory vesicle or granule with the plasma membrane and subsequent discharge of its contents is called exocytosis
42
endocytosis
1) bulk-phase: also known as pinocytosis, is the nonspecific uptake of extracellular fluids
2) receptor-mediated, brings about the uptake of specific extracellular macromolecules. it provides a means for the selective and efficient uptake of macromolecules that may be present at low concentrations. cells have receptors for the uptake of many ligans. substances that enter a cell by r.m.e. become become bound to receptors that collect in specialized domains of the plasma membrane (coated pits: receptors are concentrated in them, recognized as sites where the surface is indented and the plasma membrane is covered on its cytoplasmic face by a bristly, electron-dense coat containing clathrin).
43
phagocytosis
carried out extensively by a few types of cells specialized in the uptake of relatively large particles. many protists trap food and smaller organisms by enclosing them within fold of the plasma membrane. the folds produce a phagosome that pinches off inwardly and fuses with a lysosome, and the material is digested within the resulting complex. the engulfment is driven by contractile activities of the actin-containing microfilaments that underlie the plasma membrane.
44
post-transational uptake of proteins
1) proteins destined for a peroxisome possess a peroxisomal targeting signal.
2) most mitochondrial proteins contain signal sequences that target them to their home base. most mitochondrial matrix proteins contain a removable targeting sequence (presequence) at the N terminus. most of these proteins contain internal targeting sequences that remain as part of the molecules. the protein must be presented to the mitochondrion in a relatively extended or unfolded state. the omm (outer mito membr) contains a protein-import complex (TOM/TIM) which includes receptors that recognize and bind mitochondrial proteins and protein-lined channels. two major TIM complexes: TIM22 and TIM23. TIM22 binds integral proteins of the IMM that contain as internal targeting sequence and isnerts them into the lipid bilayer. TIM23 binds proteins with an N-terminal presequence, which includes all of the proteins of the matrix. it recognizes and translocates the matrix proteins completely through the IMM and into the inner aqueous compartment. as it enters the matrix a polypeptide interacts with mitochondrial chaperones. this mechanism is referred to as biased diffusion.
3) the vast majority of chloroplast proteins are imported from the cytosol. the outer and inner envelope contain distinct translocation complexes that work together during import. chaperones aid in the unfolding of the polypeptides in the cytosol and folding of the proteins in the chloroplast. all proteins translocated through the chloroplast envelope contain a stroma targeting domain as part of their transit peptide, which guarantees that the polypeptide will enter the stroma. once in the stroma, the targeting domain is removed by a processing peptidase.
45
cytoskeleton
it's composed of three well-defined filamentous structures (microtubules, actin filaments and intermediate filaments) that form an elaborate interactive and dynamic network.
46
microtubules
hollow, tubular structures that are assembled from the protein tubulin. they function in diverse activities (support, movement of materials). the wall of a microtubule is composed of globular proteins arranged in longitudinal rows, termed protofilaments, that are aligned parallel to the long acis of the tubule. each protofilament is assembled from dimeric builiding blocks consisting on one alpha tubulin and one beta tubulin subunit. all the protofilaments have the same polarity.
47
MAPS (microtubule associated proteins)
kinesins: they have several parts, like a pair of globular heads that bind a microtubule and act as ATP-hydrolyzing engines. each head is connected to a neck and a fan shaped tail that binds cargo to be hauled. the motor portions of all KRPs have related amino acid sequences, reflexting their common evolutionary ancestry and their similar role in moving along microtubules. their movement is hughly processive, meaning that the motor protein tends to move along an individual microtubule for considerable distances without falling off. the two heads move in a coordinated manner, so that they are always present at different stages in their chemical and mechanical cycles. the routes they followare largely defined by microtubules.
dynein: a huge protein composed of two identical heavy chains and a variety of intermediate and light chains. each chain consists of a large globular head with an elongated projection. the dynein head acts as a force generating engine. the longer projection, the stem, binds the intermediate and light chains.
48
centrosome
its where the microtubules are typically nucleated. it contains two barrel-shaped centrioles surrounded by amorphous pericentriolar material. centrioles are cylindrical structures with nine evenly spaced blades that contain three microtubules (A, B, C). only the A tube is complete. the nine A tubules are connected to a central hub. because centrosomes are sites of microtubule nucleation, the microtubules of the cytoskeleton are all polarized the same way: the minus end is associated with the centrosome, and the geowin end is situated at the opposite tip. the centrosome of a non polarized cell is tipically near the center of the cell.
49
microtubule dynamics
the ones of the mitotic spindle or the cytoskeleton are extremely labile while those of centrioles and cilia are highly stable. these differences are determined by microtubule interacting proteins which stabilize microtubules known as -TIPs, which bind to the plus end, and katanin, that severs microtubules into shorter pieces. microtubule stability is also regulated by post translational modifications to the tubulin subunits.
50
cilia and flagella
cilia tend to occur in large numbers on a cell's surface, and their beatinh activity is usually coordinated. in multicellular organisms, they move fluid and particulate maerial through various tracts. not all cilia are motile: almost all cells of the human body contain a single nonmotile cilium (primary) that is thought to have a sensory function. given the ubiquitu of cilia and their many roles in sensation and motility, their defects can lead to a range of human diseases.
flagella occur singly or in pairs and exhibit a variety of different beating patterns (waveforms), depending on the cell type. the entire ciliary or flagellar projection is covered by a membrane that is continuous with the plasma membrane of the cell. he core of the cilium, axoneme, contains an array of microtubules that runs longitudinally through the entire organelle.
51
intermediate filaments
their central building block is a pair of two intertwined helical proteins + the structure of each protein is helical (coiled-coil structure). Cytoplasmic IFs assemble into non-polar unit-length filaments which associate into antiparallel, soluble tetramers that associate into protofilaments. protofilaments pair into protofibrils, four of which wind together into an intermediate filament. The anti-parallel orientation of tetramers means that they lack polarity and cannot serve as basis for cell motility and intracellular transport.
52
actin filaments
in the presence of ATP, as a result of its subunit organization, an actin filament is a two-stranded structure with two helical grooves. all of the monomers are pointed in the same direction, resulting in a polar filament with pointed ends. before it is incorporated into a filament, an actin monomer binds a molecule of ATP. the ATP is hydrolyzed to ADP after being incorporated into a growing actin filament.
53
myosin
all myosins share a characteristic motor head domain. the head contains a site that binds an actin filament and a site that binds and hydrolyzes ATP to drive the myosin motor. myosins are generally divided into two broad groups: conventional and unconventional.
conventional: they're the primary motors for muscle contraction but are also found in a variety of non muscle cells. among their non muscle activities, they're required for splitting a cell in two during cell division. each myosin II molecule is composed of six polypeptide chains (2 heavy, 4 light) > asymmetric protein. they assemble so that the ends of the tails point towards the center. the filament is bipolar, indicating a reversal of polarity at the center.
unconventional: it serves as a cross-link between actin filaments of the cytoskeleton and the lipid bilayer of the plasma membrane. all the unconventional myosins appear to operate primarily as individual protein molecules.
54
muscle organization and contraction
muscle cells have multiple nuclei because each fiber is a product of the fusion of large numbers of myoblasts. a section of a muscle fiber reveals hundreds of thinner, cylindrical strands, myofibrils, composed of sarcomeres. each sarcomere exhibits a banding pattern: it extends from one Z line to another, and contains several dark bands and light zones. the I band contains only thin filaments, the H zone only thick filaments, and that part of the A band on either side of the H zone represents the region of overlap and contains both types of filaments. all skeletal muscles operate by shortening. as a muscle fiber shortens, the A band remains essentially constant in length, while the H and I bands decrease and then disappear. as the shortening progresses, the Z lines move inward until they come in contact with the A band.
the thin filaments are made also of troponin (contacts actin and tropomyosin) and tropomyosin (fits into the grooves of the thin filament). each thick filament is composed of hundreds of myosin II molecules.
titin: originates at the center line of each sarcomere. it's a highly elastic protein that stretches like a molecular spring as certain regions within the molecule become uncoiled. during a contraction, each myosin head extends outward and binds to a thin filament. the heads from a single muosin interact with 6 actins. the myosin undergoes a conformational change that moves the actin filament towards the center of the sarcomere. the thin filament consequently undergoes continuous motion.
55
myosin creates mechanical energy
the cycle begins as a molecule of ATP binds to the myosin head, followed by its hydrolysis, which occurs before the myosin head makes contact with actin. ADP and Pi remain bound to the active site while the energy is absorbed. the cross-bridge is in an energized state. the energized myosin attaches to the actin molecule and releases its bound phosphate > conformational change shifts the actin filament toward the center of the sarcomere. the release of ADP is followed by the binding of ATP.
56
actin binding proteins
1 > nucleating proteins : nucleation requires that at least three actin monomers come together in the proper orientation to begin formation of the polymer (unfavorable process for actin molecules left on their own)
2 > monomer-sequestring proteins : es. thymosine > bind to actin-ATP monomers and prevent them from polymerizing.conditions within the cytoplasm would favor the near complete polymerization of monomers into filaments but changes in the concentration or activity of these proteins can shift the monomer-polymer equilibrium and determine whether polymerization or depolymerization is favored at the time. they're responsible for the high concentration of monomeric actin in nonmuscle cells.
3 > capping proteins > regulate the length of actin filaments by binding to one end of the filament, forming a cap that blocks loss and gain of subunits. if the fast growing end is capped, depoly may proceed at the opposite end, resulting in the disassembly of the filament. if the pointed end is also capped, depoly is blocked.
4 > monomer-binding proteins : profilin promotes the growth of actin filaments. it does this by attaching to an actin monomer and catalyzing the dissociation of its bound ADP, which is rapidly replaced with ATP. The profilin‐ATP‐actin monomer can then assemble onto the free barbed end of a growing actin filament, which leads to the release of profilin.
5 > depolymerizing proteins bind to actin‐ADP
subunits present on the body and at the pointed end of actin filaments. two apparent activities: it can fragment actin filaments, and it can promote their depolymerization. they are essential for cell locomotion,
phagocytosis, and cytokinesis.
6 > cross-linking proteins: able to alter the three-dimensional organization of a population of actin filaments; they have two or more actin-binding sites and can cross-link two or more separate actin filaments.
7 > filament severing proteins : bind to the side of an existing filament and break it in two. may also promote the incorporation of actin monomers or cap the fragments they generate.
8 > membrane binding proteins : much of the contractile machinery of non muscle cells lies just beneath the plasma membrane. the forces generated by the contractile proteins act on the plasma membrane, causing it to protrude outwards (locomation) or inward (phagocytosis or cytokinesis).
57
the nucleus
a membrane bound organelle that contains the cell's chromosomes. it has a membrane around it that keeps all the chromosomes inside and makes the distinction between the chromosomes being inside the nucleus and the other organelles and components of the cells staying outside.
58
nuclear pore complex
it mediates transport of all macromolecules between the nucleus and the cytoplasm. its structure is a cylindrical ring-like structure lined with nucleoporins capable of binding ot transport factors. the nuclear basket is a distinct structure extending from the NPC into the nucleus. it is thought to have a role in transcriptional control, cell cycle progression. the basket seems to recruit and retain actively transcribed genes while excluding silenced heterochromatin from the transport channel. this would ensure efficient transport of messenger ribonucleoproteins into the cytoplasm. the cytoplasmic filaments interact with the protein synthesis machinery and the cytoskeleton.
59
mitosis
the replicated DNA molecules are segregated into two nuclei.
interphase > the two uncondensed sister chromatids are bound together thanks to a protein called cohesin. the cell has also a copy of its centrosome.
prophase > the cell starts to break down some structures and build other up. the chromosomes start to condense and the mitotic spindle begins to form. the spindle is a structure made of microtubules. the nucleolus disappears: this is a sign that the nucleus is getting ready to break down.
prometaphase > the mitotic spindle begins to capture and organize the chromosomes, which have become even more condensed and compact. the nuclear envelope breaks down, releasing them. the mitotic spindle grows more, and some of the microtubules start to capture chromosomes. microtubules can bind to chromosomes at the kinetochore, a patch of protein found on the centromere of each sister chromatid. microtubules that bind a chromosome are called kinetochore microtubules. microtubules that don't bind to kinetochores can grab on to microtubules from he opposite pole, stabilizing the spindle. more microtubules extend from each centrosome towards the edge of the cell, forming the aster.
metaphase > the spindle has captured all the chromosomes and lined them up at the middle of the cell. all the chromosomes align at the metaphase plate. the two kinetochores should be attached to microtubules from opposite spindle poles. before proceeding to anaphase, the cell will check to make sure that all the chromosomes are at the plate with the kinetochores. this is the spindle checkpoint (if a chromosome is not properly aligned or attached, the cell witll halt division until the problem is fixed)
anaphase > the sister chromatids separate from each other and are pulled towards opposite ends of the cell. the movement towards the poles is referred to as anaphase A. in anaphase B the two spindle poles move farther apart. the protein glue that holds the sister chromatids together is broken down. microtubules not attached elongate and make the cell longer. all these processes are driven by motor proteins, molecular machines that can walk along microtubule tracks and carry cargo.
telophase > the cell is almost done dividing and it starts to re-establish its normal structures as cytokinesis takes place. the mitotic spindle is broken down into its builing block. two new nuclei form, one for each set of chomosomes. nuclear membranes and nucleoli reappear. the chromosomes begin to decondense and return to their stringy form. cytokinesis > overlaps with the final stages of mitosis. in animal cells it's contractile, pinching the cell in two (cleavage furrow). plant cells can't be divided like this because they're too stiff. a structure called the cell plate forms down the middle of the cell, splitting it into two daughter cells separated by a new wall.
60
genetic diversity in mitosis
1 > independent assortment : the orientation of homologous chromosome pairs along the plate and the subsequent separation of chromatids allows a random and independent distirbution of chromosomes to each daughter cell
2 > crossing over : the physical exchange of homologous chromosomal regions by recombination results in new combinations of DNA within chromosomes.
61
prophase of meiosis
leptotene > two sister chromatids condense into long thin strands. they're so tightly bound that they are not distinguishable from one other. this stage is very short. the nucleolus disappears.
zygotene > chromosomes line up to form homologous chromosome pairs. this stage is known as bouquet stage, as telomeres cluster at one end of the nucleus. one feature is synapsis of homologous chromosomes. synapsis is facilitated by the assembly synaptonemal complex. pairing of chromosomes occurs in a zipper like fashion. two chromosomes in a pair are qual in lenght and position of the centromere, making the pairing highly specific and exact. these paired chromosomes are called bivalent. the centrosome divides into two equal halves.
pachytene > the chromosomes condense further and become distinct, shorter and thicker. the two sister chromatids of each homologous chromosome become clearly visible. the bivalent thus become a tetrad with four chromatids. this is the stage where chromosomal crossing over occurs. in the region of the chiasmata, segments of non sister chromatids of the homologous chromosomes are exchanged. this results in recombination. every chromosome now has a complete set of information and all the gaps are removed by the end of this process.
diplotene > during this stage the synaptonemal complex gets degraded and due to this degradation the homologous chromosomes separate from each other except at the chiasmata. this region remains on the chromosomes until they are separated in the fetal stage stop.
diakinesis > the chromosomes continue to contract. the separation becomes complete due to terminalisation. the separation starts from the centromeres and foes towards the end. the nucleolus and nuclear membrane disappear. the formation of spindles starts from the centrioles of centromeres.
62
meiosis I
metaphase I > the nuclear membrane disappears, centrioles reach the opposite. the spindle fibers become prominent and get connected to the centromere of the homologous chromosomes. the bivalents align on the equatorial plane.
anaphase I > the two chromosomes of each bivalent with chromatids still attached to the centromere separate from each other and move to the opposite poles of the cell. thus, only one chromosome of each homologous pair reaches each pole. consequently at each pole only half the number of chromosomes is received.
telophase > reorganization of the chromosomes at poles occurs to form two haploid nuclei. nuclear membrane is reformed around the polarized groups of chromosomes. nucleolus also re-appears, while the spindle disappears. the cell membrane constricts and two daughter cells are formed.
63
meiosis II
the result is four haploid cells (n chromosomes) from the two haploid cells (with n chromosomes, each consisting of two sister chromatids).
prophase II > chromosomes condense and the nuclear envelope breaks down if needed. the centrosomes move apart, the spindle forms between them, and the spindle microtubules begin to capture chromosomes. the two sister chromatids of each chromosome are captured by microtubules frome opposite spindle poles.
metaphase II > the chromosomes line up individually along the metaphase plate
anaphase II > the sister chromatids separate and are pulled towards opposite poles of the cell
telophase II > nuclear membranes form around each set of chromosomes, and the chromosomes decondense. cytokinesis splits the chromosome sets into new cells, forming the final products of meiosis: four haploid cells in which each chromosome has just one chromatid
64
glyco alix > extracellular interaction
carbohydrate projections: all integral membrane proteins, as well as certain membrane lipids, bear chains of oligosaccharides of variable lenght that project outward from the plasma membrane.
65
collagens
collagens are secreted by connective tissue cells (fibroblasts), smooth muscle cells and epithelial cells. they are the most abundant proteins in mammals. they're noted for their hight tensile to pulling forces.
the corneal stroma is organized in distinct layers, in which the fibrils of each layer are parallel to the others of the same layer, but perpendicular to the fibrils of the adjacent layers. this organization gives resistance to the tissue, the uniformity of the dimensions and the ordered arrangement of the fibrils almost completely cancel the dispersion of the incident light rays and determines the transparency of the tissue. collagen is highly crosslinked in tissues where tensile strenght is required if cross-linking is inhibited, the tensile strenght of fibers is greatly reduced, collagenous tissues become fragile and structures tend to tear.
66
elastin
a highly hydrophobic protein, main component of elastic fibers. soluble tropoelastin (biosynthetic precursor) is secreted into ECM and assembled into elastic fibers close to the plasma membrane. after secretion, the tropoelastin molecules become highly crosslinked to one another, generating an extensive network of elastin fibers and sheets.
67
proteoglycans
consist of a core protein molecule to which chains of glycosaminoglycans ( GAGs ) are covalently attached. each GAG chain is composed of a repeating disaccharide; it has structure ABAB, where A and B represent two different sugars. GAGs are highly acidic due to the presence of both sulfate and carboxyl groups attached to the sugar. because of the negative charges born on the sulfated GAGs, proteoglycans bind huge numbers of cations, which in turn bind large numbers of water molecules.
68
fibronectin
consist of a linear array of domains. each of the two polypeptide chains that make u a fibronectin molecule contains binding sites from components of the matrix (facilitate interactions that link these molecules into a network) and binding sites for receptors on the cell surface.
69
laminin
a family of extracellular glycoproteins that consist of three different polypeptide chains linked by disulfide bonds. in addition to binding tightly to cell surface receptors, they can bind to other laminin molecules, proteoglycans, and to other components of basement membranes. fibronectin and laminin can bind specific receptors on the cell surface. these receptors belong to a family of transmembrane proteins called INTEGRINS because they have the role of integrating the EMC with the cytoskeleton. they are also implicated in signal transmission between intracellular and extracellular environments in both directions. alteration in integrin affinity triggered by changes occurring inside the cell is referred to as inside out signaling.
70
focal adhesions
large macromolecular integrin-containing assemblies. they are in a state of constant flux: proteins associate and disassociate with them continually as signals are transmitted to other parts of the cell. they form mechanical links between itnracellular actin bundles and the extracellular substrate. they are capable of creating mechanical forces or responding to such forces. mechanical forces can be converted into biochemical signals in the cytoplasm (mechanotransduction; thought to be mediated by conformational changes in some of the adaptor proteins)
71
hemidesmosomes
very small structures found in keratinocytes (primary type of cell of the skin) that attach to basal membrane. contain a dense plaque on the inner surface of the plasma membrane with filaments coursing outward into the cytoplasm.
72
cellular adhesion molecules
selectins > all three types of known selectins recognize and bind to a similar carbohydrate ligand at the ends of oligosaccharide chains on glycoproteins. they mediate transient interactions between circulating leukocytes and vessel walls at sites of inflammation and clotting
lgSF > most of them mediate the specific interactions of lymphocytes with cells required for an immune response.
cadherins > three types: epithelial, neural and placental. they contain a relatively large extracellular segment and a small cytoplasmic domain. different types of cells bearing different cadherins likely engage in different types of interaction, so that many different configurations may occur within an organism. they're thought to mediate many of the dynamic changes in adhesive contacts that are required to construct the tissues and organs on an embryo
73
adhesive junctions and desmosomes
robust mechanical junctions made possible by membrane proteins that interact at an interstitial level with those of the adjacent cell. they are particularly common in epithelia. desmosomes are disk‐shaped adhesive junctions particularly numerous in tissues that are subjected to mechanical stress, such as cardiacmuscle. desmosomes contain cadherins that link the two cells across a narrow extracellular gap. these cadherins are referred to as desmogleins
74
tight junctions
a seal that prevents the passage of substances between the extracellular apical domain and the basolateral domain. they're located at the very apical end of the junctional complex between adjacent epithelial cells. the point of cell-cell contact sites where integral proteins of two adjacent membranes meet within the extracellular space. TJs are found in the intestinal epithelium, in ducts and glandular cavities that connect the liver and the pancreas to the intestine and in the bladder
75
gap junctions
allow the passage of small molecyles between adjacent cells. they're composed of an integral membrane protein called connexin. 6 connexins, arranged in a ring around a central opening, the annulus, are organized into multisubunit complexes called connexons
76
signal transduction
autocrine signaling > the cell that is producing the messenger expresses receptors on its surface (cells releasing the message will stimulate / inhibit themselves)
paracrine signaling > messenger molecyles travel only short distances through the extracellular space to cells that are in close proximity to the cell that is generating the message.
endocrine signaling > messenger molecules reach their target cells via passage through the bloodstream.
the interaction induces a
77
g protein coupled receptors
seven transmembrane alpha helices. these receptors translate the binding of extracellular signaling molecules into the activation of GTP-binding proteins. amino terminus is present on the outside of the cell, the 7 alpha helices that traverse the plasma membrane and the carbozyl - terminus are present on the inside of the cell. there are three loops present on the outside of the cell that form the ligand binding pocket, whose structure varies among different receptors. once activated, GPCRs induce signals at the cell surface. this is often followed by internalization, a process that results in the transfer of receptors from the plasma membrane to membranes of the endosomal compartment.
78
receptor protein-tyrosine kinases (RTKs)
binding of a specific ligand to them usually results in receptor dimerization followed by activation of the receptor's protein-kinase domain.
79
2nd messengers
conformational change in the receptor that causes the signal to be relayed across the membrane to the receptor's cytoplasmic domain. one type of receptor transmits a signal from its cytoplasmic domain to a nearby enzyme (effector), which generates a second messenger. they are typically present at low concentrations in resting cells and can be rapidly produces or released when cells are stimulated. the levels of second messengers are controlled temporally during signaling. these messengers then diffuse rapidly from the source and bind to target proteins to alter their properties to propagate signaling.
80
MAPK
the MAPK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. the signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some changes in the cell, such as cell division. the pathway includes many proteins including MAPK (mitogen-activated protein kinases), which communicate by adding phosphate groups to a neighboring protein (phosphorylating it), which acts as an "on" or "off" switch. When one of the proteins in the pathway is mutated, it can become stuck in the "on" or "off" position, which is a necessary step in the development of many cancers.
81
cyclic AMP (cAMP)
cyclic adenosine monophosphate. adenylyl cyclase converts ATP into cAMP, removing two phosphates and linking the remaining phosphate to the sugar in a ring shape. once generated, cAMP can activate an enzyme called protein kinase A (PKA) enabling it to phosphorylate its targets and pass along the signal. cAMP signaling is turned off by enzymes called phosphodiesterases, which break the ring of cAMP and turn i into adenosine monophosphate (AMP)
82
cyclin dependent kinases
Cyclins are a group of related proteins, and there are four basic types found in humans and most other eukaryotes: G1 cyclins, G1/S cyclins, S cyclins and M cyclins. A typical cyclin is present at low levels for most of the cycle, but increases strongly at the stage where it’s needed. G1 cyclins are unusual in that they are needed for much of the cell cycle.
cyclins drive the events of the cell cycle by partnering with a family of enzymes called cyclin dependent kinases (CDKs). a lone CDK is inactive but the binding of a cyclin activates it, making it a functional enzyme and allowing it to modify target proteins. CDKs are kinases, enzymes that phosphorylate specific target proteins. the attached P group acts like a switch, making the target protein more or less active. when a cyclin attaches to a CDK, it activaes the CDK and directs is to a specific set of target proteins, ones appropriate to the cell cycle period controlled by the cyclin. Cdk must also be phosphorylated on a particular site in order to be active and may also be negatively regulated by phosphorylation of other sites.
83
checkpoints
THE G1 CHECKPOINT > is the main decision point for a cell. Once the cell passes it, it becomes irreversibly committed to division.
THE G2 CHECKPOINT > the cell checks DNA integrity and DNA replication (was the DNA completely copied during S phase?).
THE M CHECKPOINT > is also known as the spindle checkpoint: there the cell examines whether all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids is an irreversible step, the cycle will not proceed until all the chromosomes are firmly attached to at least two spindle fibers from opposite poles of the cell.
84
regulators
they respond to cues from inside and outside the cell. these cues influence activity of the core regulators to determine whether the cell moves forward in the cell cycle. positive cues increase the activity of CDK and cyclins, while negative ones decrease or block activity. key to DNA damage response is p53, a tumor suppressor often described as the guardian of the genome. p53 works on multiple levels to ensure that cells do not pass on their damaged DNA through cell division. first it stops the cell cycle at the G1 checkpoint by triggering production of CDK inhibitors (CKI) proteins. the CKIs bind to CDK-cyclin complexes and block their activity. they also activate DNA repair enzymes. if DNA damage is not fixable, p53 will trigger apoptosis.
85
death receptor pathway
it's activated by external cytokinesis and is mitochondria-independent. the lifands of the death receptors are members of the TNF family. binding of ligands results in homo trimerization (3 molecules = one trimer) of the receptor. they contain a death domain that's required for apoptosis signaling. trimerization of the death receptor domain allows binding and activation of FADD (fas associated death domain proteins) and formation of the death inducing signaling complex.
86
apoptosis
it occurs on a cell-by-cell basis. two phases (initiation and execution) and two families of proteins. the BCL-2 proteins provide the framework for controlling apoptosis. the caspase proteolytic enzymes contribute to both regulation and execution of apoptosis. the cellular destruction occurs in situ, and the cellular membrane system is reorganized to package the degraded components, including the digested genetic material.
87
apoptosis pathways
intrinsic > cytochrome c is released from mitochondria and binds with apaf 1 (apoptotic protease activating factor 1) and ATP, which then bind to pro-caspase-9 to create the apoptosome. this cleaves the caspase to caspase 9 and then caspase 3, which activates DNase. DNase causes degradation of chromosomal DNA within the disintegration of cells into apoptotic bodies. mitochondria also release proteins known as SMACs (second mitochondria derivedactivator of caspases) into the cell's cytosol following the increase in permeability of the mitochondrial membranes. SMACs bind to proteins that inhibit apoptosis and prevent them from arrestinf the process.
extrinsic pathway > begins outside a cell, when conditions in the extracellular environment determine that a cell must die. death receptors activate the apoptosis: their death domains activate two procaspases-8, which cut their respective inhibitory domains and become caspases-8. these are able to cut the inhibitor domain of procaspase-3 > caspase 3 activates caspase 9 > cascade activated.
88
necrosis
it's an uncontrolled and passive process that usually affects large fields of cells. necrotic cell injury is mediated by two main mechanisms; interference with the enrgy supply of the cell and direct damage to cell membranes. some of the major morphological changes that occur with necrosis include cell swelling, formation of cytoplasmic vacuoles, distended endoplasmic reticulum, formation of cytoplasmic blebs and eventually disruption of the cell membrane. this loss of cell membrane integrity results in the release of the cytoplasmic contents into the surrounding tissue, sending chemotatic signals with eventual recreuitment of inflammatory cells.
89
necroptosis
a programmed form of necrosis. it's defined as a viral defense mechanism, allowing the cell to undergo cellular suicide in a caspace independent fashion. an extrinsic signaling ligans binds to TNF. this leads tro the recruitment of a complex, called the prosurvival complex I, composed of TNF receptor associated death domain, polyibiquitinated RIPK1 and ubiquitin E3 ligases. RIPK1 dissociates > complex IIa or IIb. IIa is involved in the activation of caspase 8 activation, which leads to apoptosis. IIb is necroptosis and is fored when caspase 8 is inhibited. RIPK1 recruites RIPK3 and they phosphorylate each other > oligomerization and necrosome formation. the necrosome phosphorylates MLKL, which inserts into the membrane and permeabilizes it > necroptosis. the internal celllar components are then released, which triggers inflammation and the acquired immune response > pinocytosis
90
stem cells
cells with the potential to develop into many different types of cells in the body. they serve as a repair system for the body. there are two main types: embryonic and adult. embryonic are pluripotent. as the body develops and ages, the number and type of stem cells changes. totipotent cells are no longer present after dividing into the cells that generate the placenta and umbilical cord. pluripotent cells give rise to the specialized cells that make up the body's organs and tissues. the stem cells that stay in the body are tissue specific.
