Unit 3 Study Guide
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This 21 page Study Guide was uploaded by David Edwards on Wednesday May 18, 2016. The Study Guide belongs to BIO 204 at MiraCosta College taught by S. Bailey in Spring 2016. Since its upload, it has received 15 views. For similar materials see Metabolic Biochemistry in Biology at MiraCosta College.
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Date Created: 05/18/16
Autocrine membrane of a neuron Gated Ion Channel Autocrine signaling is a A gated channel for a form of cell signaling in specific ion which a cell secretes a Insulin The opening or closing may hormone or chemical A hormone secreted by alter a cells membrane messenger that binds to pancreatic beta cells that potential. autocrine receptors on that lowers blood glucose Steroid Hormone Receptor same cell, leading to levels. Intracellular receptor changes in the cell. Promotes the uptake of protein found in the Paracrine glucose by most body cells cytoplasm of target cells. Numerous cells can and synthesis and storage Hormones are hydrophobic simultaneously receive and of glycogen in the liver and and can pass through respond to the molecules of also stimulates protein and target cell membranes and growth factor produced by fat synthesis bind to a receptor in the a single cell in its vicinity Glucagon cytoplasm or nucleus Endocrine A hormone secreted by turning on/off genes Specialized cells release pancreatic alpha cells that Second Messenger hormone molecules which raises blood glucose levels. A small nonprotein, water travel via the circulatory Promotes glycogen soluble molecule or ion , system to other parts of the breakdown and release of such as calcium ions body where they reach glucose by the liver (Ca2+) or cyclic AMP, that target cells that can Gprotein Coupled Receptor relays a signal to a cell’s recognized and respond to A signal receptor protein in interior in response to a the hormones. the plasma membrane that signaling molecule bound Synapse Neurotransmitter responds to the binding of by a signal receptor Local signaling occurring in a signaling molecule by protein. the nervous system of activating a G protein. G protein animals where an electrical Receptor Tyrosine Kinase A GTPbinding protein that signal along a nerve cell A receptor protein spanning relays signals from a triggers the secretion of plasma membrane signal the plasma membrane, the neurotransmitter cytoplasmic part of which receptor, known as a G molecules. can catalyze the transfer of Proteincoupled receptor, The neurotransmitters act a phosphate group from to other signal transduction as chemical signals ATP to a tyrosine on proteins inside the cell diffusing across the another protein Adenylyl Cyclase synapse—the narrow Often respond to the An enzyme that converts space between the nerve binding of a signaling ATP to cyclic AMP in cell and its target cell— response to an extracellular molecule by dimerizing and triggering a response in the then phosphorylating a signal target cell. tyrosine on the cytoplasmic Cyclic AMP Action Potential portion of the other cAMP is a ringshaped An electrical signal that receptor in the dimer molecule made from ATP propagates along the that is a common has moved along the signaled by other cells intracellular signaling membrane after activate by sending messengers to bind molecule (2 messenger) a glucagon receptor binds to death receptors on that in eukaryotic cells. with a glucagon molecule cell telling it to kill itself. Regulator of some bacterial Phosphotidyl Inositol Caspase operons. Bisphosphate (PIP2) Proteases that mediate apoptosis by degradation of A plasma membrane phospholipid that is cleaved cytoskeletal fibers and off by PLC to become DAG nuclear lamina proteins Dictyostelium (secondary messenger) and Schmooing IP3 A cellular slime mold The elongation of yeast commonly found on forest cells once mating between floors Inositol Triphosphate (IP3) an a and an yeast Model organism for A secondary messenger molecule begin. studying evolution of that comes from a Derived from a ‘40s cartoon multicellularity phospholipid cleaved off by character that looks like Fruiting body stage where PLC that diffuses through elongating yeast. cells that form the stalk die the cytosol and binds to a Yeast Mating Factors as they dry out, while the gated ion channel on the a and yeast molecules spore cells at the top smooth ER to allow Ca2+ to send amorous signals to survive and have the flow out. each other in the form of potential to reproduce Epinephrine/Adrenaline small peptides that bind to Phosphodiesterase Fight/flight hormones receptors to attract one to An enzyme that converts released from the adrenal the other to being mating cAMP to AMP medulla Fus3 Glucose Transporter Voluntary muscle A kinase in the signaling (GLUT4) contractions when secreted cascade that is activated by Vesicles that move to the by neurons as a a GPCr for mating factors plasma membrane to take neurotransmitter of yeast G Protein coupled receptor Formin in glucose and bring into the cell after a kinase cascade binder that signals the A target of phosphorylation activated by an RTK release of glycogen of Fus3 which is a protein Glycogen Phosphorylase phosphorylase to release that directs microfilament glucose for energy Enzyme that construction phosphorylates a glycogen Adrenergic Receptor Receptor Mediated molecule to cleave off a A GPCr that is the binding Endocytosis glucose molecule to be site for To terminate a signal, epinephrine/adrenaline used for energy certain cell receptors move Phospholipase C (PLC) hormone molecules. out of the plasma Plasmabound enzyme that Apoptosis membrane and into the allosterically activates the G Programmed cell death in cytoplasm of the cell to ProteinDTP complex that an organized way usually prevent binding of more signals mitosis. Quiescent Clathrin Cellular metabolic activity is Cell is at a dormant state high, chromosomes and a basketlike network of Mitotic Phase protein molecules that forms organelles are duplicated, The shortest part of the on the cell membrane in and cell size will increase cell cycle where the cell is response to the attachment G1 undergoing division, of ligands to receptors and st 1 gap phase, or growth divided into 7 different becomes the inside surface phase, of the phase before steps. of the coated vesicle during DNA synthesis begins. Mitosis endocytosis. Protein synthesis, glycolysis Asexual reproduction of Binary Fission and specialized functions cells to produce genetically Simple division for simple start to occur and develop. identical daughter cells organisms such as Sphase Keeps track and prokaryotes Synthesis phase where segregates multiple linear Circular DNA in nucleoid is DNA replication occurs chromosomes replicated and an Diploid forms with For singlecelled invagination splits the cell chromatids form and are Eukaryotes (ie Yeast) this exactly in half through is propagation held together by cohesins membrane and cytoplasm o Diploid is a cell with 2 For multicelled Asexual Reproduction sets of genetic Eukaryotes this is growth, The generation of offspring information repair, and replacement. from a single parent that 2(n)=4 in a occurs without the fusion of diploid cell with Prophase/Prometaphase gametes. 2 chromosomes Centrosomes form where Offspring are genetically o Chromatids are microtubules will grow out identical to the parent from identical copies of from. budding, division of single chromosomes from DNA condensation and cell, or division of the entire DNA replication organization into tightly organism into two or more o Cohesins are ring paired sister chromatids parts proteins that hold Reorganizing of Sexual Reproduction chromatids together microtubules into a spindle Type of reproduction in G2 structure which two parents give rise 2 Gap phase where cell Centromere region on sister to offspring that have growth occurs, organelles chromatids are designated unique combinations of duplicate, and DNA is still held together by genes inherited from both repair at any points of cohesins where kinetochore parents via the gametes damage before entering is assembled for Interphase mitosis microtubules to interact with G1, Sphase, and G2 phase G0 Metaphase when cell prepares for The phase the cell enters Chromosomes align at cell division by growing in size, after G1 if it repeats and equator awaiting motor copying chromosomes, and does not enter interphase proteins to pull microtubules grows more to prepare for to separate sister found in the G1, G2, and Kinases that drive the cell chromatids. Mitosis phases cycle must be attached to Anaphase Growth Factor cyclin to be active. Sister chromatids are A local regulator that acts Cyclin Dependent Kinase separated by “walking” on nearby cells to stimulate Kinase that is dependent on motor proteins along cell proliferation and cyclin to be activated. microtubules which are differentiation. Activity of a Cdk rises and connected to kinetochores. DensityDependent falls with changes in the Telophase (Contact)Inhibition concentration of its cyclin Reversal of An external physical factor partner prophase/prometaphase. on cell division that tells Mitosis Promoting Factor Two daughter nuclei form crowded cells to stop CyclinCdk complex that with nuclear envelopes dividing triggers the cell’s passage Chromosomes are less Anchorage Dependence into the mitotic phase past condensed and spindle A characteristic of animal the G2 checkpoint fibers are removed. cells where in order for When cyclins that Cytokinesis them to divide, they must be accumulate during G2 Division of cytoplasm to attached to a substratum associate with Cdk create 2 identical daughter such as extracellular matrix molecules, the resulting cells ready to enter G1 of a tissue MPF complex Kinetochore Anchorage is signaled to phosphorylates a variety of the cell cycle control system proteins, initiating mitosis. Protein structure at the sister chromatids via pathways involving Cdc25 centromere region where plasma membrane proteins Phosphatase enzyme that spindle microtubules and elements of the removes a phosphate group connect. cytoskeleton linked to them. from a cyclincdk complex in Centrosomes/Microtubule order to activate it and send Organizing Center Tumor the cell into prophase from The structures made of A mass of abnormal cells G2. within otherwise normal Inhibited until DNA is done centriole pairs where microtubules stem from to tissue. replicating form spindle fibers Cells grew from one cancer Wee1 Centromeres cell that was not eliminated Kinase enzyme that by the immune system. Region on sister chromatids phosphorylates a cyclincdk where kinetochores form to Metastasis complex while DNA repair allow microtubules to The spread of cancer cells and cell growth are still going attach. to locations distant from the on. Cell Cycle Checkpoint original site. Also acts as regulator to Control point in the cycle Cyclin keep cyclincdk inactive after where and stop and go Protein that gets it s name cdc25 removes a phosphate ahead signals can regulate from its cyclically fluctuation if cell is “not ready” to enter prophase the cycle. Checkpoints are concentration in the cell. Condensin eukaryotic cell division. condition. Enzymes that play a role in The primary function of Karyotype chromatin is to compress the condensing DNA strands the number and appearance into more organized DNA into a compact unit that of chromosomes in the chromatids will be less voluminous and nucleus of a eukaryotic cell. Microtubule Associated can fit within the nucleus. Gamete/Germ Cell Chromatid Proteins a cell that fuses with Any proteins associated with Identical copies of another cell during microtubules including chromosomes from DNA fertilization in organisms myosin motor proteins and replication that sexually reproduce. tubulin subunits that connect Chromosome Somatic Cell to create microtubule a packaged and organized any cell of the body except stability. structure containing most of sperm and egg cells. Cohesin the DNA of a living Somatic cells are diploid, Ring protein that holds organism. It is not usually meaning that they contain sister chromatids together. found on its own, but rather two sets of chromosomes, Anaphase Promoting is structured by being one inherited from each Complex wrapped around protein parent. A complex activated complexes called Homolog allosterically by the tension nucleosomes, which consist Chromosomes of the same sensing protein CDC20 in of proteins called histones. type; one inherited from Meiosis each parent the kinetochore at the spindle assembly A reductive division of germ Allele checkpoint. cells (sperm and eggs) in Alternate versions of the Ubiquitin ligase is the sexually reproducing same gene that arise from organisms including enzyme activated that binds mutations. to either securins or cyclin multi/singlecelled Gene If Ub binds to securins, eukaryotes a locus of DNA that cohesins are cleaved so Diploid encodes a functional RNA A cell with 2 sets of sister chromatids can be or protein product, and is separated leading to chromosomes the molecular unit of anaphase Haploid heredity. If Ub binds to cyclin the the term used when a cell Chiasma has half the usual number of cyclinCdk complex is the point where inactivated and this leads to chromosomes. two homologous nonsister telophase. A normal eukaryote chromatids exchange Chromatin organism is composed of genetic material diploid cells, one set of Chromatin is a mass of during chromosomal genetic material composed chromosomes from each crossover in meiosis of DNA and proteins that parent. However, after but because their genetic condenses to form meiosis, the number of material is identical, it does chromosomes in gametes is chromosomes during not cause any noticeable halved. That is the haploid change in the resulting tetrads switch bits of DNA at because one parent passes daughter cells different breakpoints the allele which may be Synapsis causing deletion and masked by the dominant The connection of homolog duplication which may lead allele pairs that form a tetrad to increased diversity and Gain of Function Mutation during the prophase of number of genes in A type of mutation in which Meiosis 1. duplication the altered gene product Tetrad Truebreeding possesses a new The structure of 4 homologs An organism that will always molecular function or a new that form during the pass down certain pattern of gene expression. phenotype expressions to Loss of Function Mutation synapsis of prophase in Meiosis 1. its offspring also called inactivating Recombination Homozygous mutations, result in the gene When sister chromatids A genotype expressed as product having less or no switch for new combo of two of the same genes, one function (being partially or alleles during prophase of from each parent—either wholly inactivated). Meiosis 1. both dominant or both Codominant Independent Assortment recessive a cross between organisms Heterozygous The alignment of tetrads with two different independent of one another A genotype expressed as phenotypes produces during metaphase of two different genes, one offspring with Meiosis 1 allowing for from each parent—one a third phenotype in which different combinations of dominant and one both of the parental traits alleles. recessive. appear together. Nondisjunction Test Cross Incomplete Dominance When a homolog does not Dominant a cross between organisms separate from a tetrad The gene that is expressed with two different during anaphase in Meiosis regardless of the other phenotypes produces 1 and the whole tetrad allele—ie Aa or AA where A offspring with moves to one side when the is the dominant allele a third phenotype that is microtubules pull the In trait inheritance, there are a blending of the parental homologs to opposite sides no silent carriers are traits. via motor proteins. possible because both Pleiotropy Trisomy parents have at least 1 When one gene affects the A condition of a zygote due allele outcome of more than one to nondisjunction of a Recessive phenotype gamete after fertilization The gene that is not Epistasis causing an extra chromatid expressed unless it is A gene that is expressed in the zygote. Leads to paired with another that can block the apoptosis. recessive allele (one from expression of other Nonreciprocal Crossover each parent. phenotypes During recombination In trait inheritance, there Polygenic can be silent carriers When multiple genes affect XY=male expressed. the outcome of one Maternal Inheritance XInactivation phenotype expression Inheritance of a phenotype In women, one X Autosome that is linked to the X chromosome is condensed Any chromosome that is not chromosome passed down and most genes on it are associated with the sex from mother to offspring. inactivated to compensate for gene dosage (2 Xs). chromosomes (X Imprinting chromosome) certain genes are This way the number of Sex Chromosome Linkage expressed in a parentof genes is equal in XX and A gene associated with the originspecific manner. If the XY Reciprocal Cross last of the 23 chromosomes allele inherited from the that expresses the sex in an father is imprinted, it is During Meiosis Prophase I, organism. thereby silenced, and only tetrads switch some bits of XX=female the allele from the mother is DNA at specific break points 1.Why is cellular communication critical for both unicellular and multicellular life forms? Provide a specific example that illustrates the importance to both. Cellular communication is critical for both unicellular and multicellular organisms because it is the way organisms react to stimuli. For unicellular organisms such as yeasts, it is essential that yeast mating factors are used to communicate with a and sexes so the organisms can come together and procreate. For multicellular organisms, reacting in a fight/flight way is key to survival. When a muscle needs to move or glucose must be released from glycogen storage to use for energy to provide cells with ATP, it is celltocell communication that uses neurons and GPC receptors respectively to trigger the responses. 2.In general, what crucial function in the cellular communication process is associated with receptors? What are the four main types of receptors we discussed and how do they differ in carrying out this crucial function? Cell to cell signaling is the crucial function in the cellular communication to trigger hormone secretions, ion gradient generation, and/or neurotransmitter release. Intracellular receptors are used for nonpolar ligands (ie hormones or nonpolar gases) because the receptor is inside the cell cytoplasm with a chaperone bound to it. The hormone enters the cell and the chaperone unbinds and the receptorhormone complex is now able to enter the nucleus and bind to DNA. This changes the protein profile and a new transcription is directed (hormones are transcription factors). Membraneembedded receptors such as gated ion channels receive a signal via a ligand that binds to the receptor to trigger a response such as a channel that opens and closes to allow a glow of ions (ie Ach receptor). In this example vesicles with Ach leave the nerve cell and bind to a receptor as neurotransmitters. This allows Na+ to enter the cell causing a change in the charge which opens a gated Ca+ channel at the smooth ER. The Ca+ flows out and signals muscle contraction by myosin binding to actin microfilaments. G Protein Coupled Receptors (GPCr)use G proteins which are enzymes that bind to and hydrolyze GTPGDP and P. GPCi is a transmembrane protein that passes through the membrane seven times. It is bound to a G protein inside the cell along the cell membrane and when a ligand binds, the GDP that is bound to the G protein cleaves off and a GTP attaches. The G proteins and GTP move along the cell membrane to an enzyme that is activated allosterically. The enzyme then catalyzes a product that acts as a 2 messenger that diffuses through cytoplasm to activate other enzymes and a phosphorylation chain to trigger a cell response such as glycogen phosphorylase to release glucose from glycogen stores. Receptor Tyrosine Kinases (RTKs) are membrane embedded receptors that have a tyrosine kinase enzyme that extends into the cytoplasm of the cell. This part of the protein functions as an enzyme that catalyzes the transfer of a phosphate group from ATP to the amino acid tyrosine on a substrate protein. One RTK may activate ten or more transduction pathways and cellular responses. More than one pathway can be activated at once, helping the cell regulate and coordinate many aspects of cell growth and cell reproduction. Ligands bind to the receptors causing dimerization of two receptors and cross phosphorylation occurs activating a kinase cascade leading to the cellular response. 3.What class of signaling molecules bind to intracellular receptors? What chemical property do they share that makes this possible? What is the “typical” cellular response induced by these signaling ligands? Hormones are the signaling molecules that bind to intracellular receptors. Because they are nonpolar they can pass through the plasma membrane and diffuse through the cytoplasm and then again pass through the nuclear envelope to the receptors. The steroid hormone binds to a receptor protein either in the cytoplasm or nucleus after passing from the gland it is secreted from through the blood stream to a target. The hormone binds to specific genes in the nucleus and acts as a transcription factor, stimulating the transcription of the gene into mRNA. The mRNA is translated into a specific protein. 4.What is a second messenger? In general, what crucial function in the cellular communication process is associated with second messengers? Second messengers are small nonprotein, watersoluble molecules or ions. The first messenger is usually the ligand that binds to the first receptor. The secondary messenger usually diffuses through the cytoplasm quickly to the next receptor that may be a kinase cascade to trigger a cellular response. Secondary messengers participate in pathways that are initiated by both G proteincoupled receptors and RTKs and the most widely used are cAMP and calcium ions. 5.What are heterotrimeric G proteins? Why are they referred to as heterotrimeric? Why are they called G proteins? Heterotrimeric G proteins are enzymes that bind to and hydrolyze GTP—GDP +P. They arei bound to GPCr at the plasma membrane in the cytoplasm. They are referred to as heterotrimeric because they are three different proteins structures all bound together to create one large enzyme. They are referred to as G proteins because they hydrolyze GTP after they release a bound GDP molecule and move along the plasma membrane to an enzyme. 6.How is activation of a G protein accomplished? How does the transition from inactive to active and then back to inactive state occur? A G protein is activated when a ligand binds to the GPCr at the plasma membrane. This causes a bound GDP molecule to be cleaved off and a GTP molecule binds causing it to move along the cell membrane to an enzyme which it activates allosterically. The enzyme then catalyzes a product and a Pi is cleaved off leaving a GDP bound the the G protein which returns to its bound GPCr to wait for another ligand to trigger it. 7.How is it correct to refer to G protein activation as “selfdeactivating”? Why is it important that they operate this way? What would be the consequence if they didn’t? G proteins are selfdeactivating in that they hydrolyze the GTP to GDP and Pi that bound to it to activate it in the first place. The GPCr also goes under endocytosis to move into the cell and out of its membranebound position. This is important because it prevents further ligands to bind to the receptor and, therefore, further activation of the Gprotein that would, in turn, keep activating the kinase cascade to initiate a cell response. If this didn’t happen the consequence would be continued activation, which, for a response such as the adrenaline/epinephrine, could cause a drain on the glycogen storage in the body. 8.How does ligand binding lead to activation of receptor tyrosine kinases? How is this fundamentally different mechanistically from GPCR activation? Ligands bind to two membranebound receptors with a structure that passes through the membrane to an enzyme complex in the cytoplasm. The ligands of the same type must both bind to the receptors and the RTKs dimerize through cross phosphorylation. This activates a kinase cascade leading to a cell response. This is different than GPCr activation in that it requires two structures to be activated and the receptor is actually an enzyme itself. When the structures are phosphorylated, specific, activated relay proteins can bind to the complex, change shape, and then activate a transduction pathway leading to cellular response. Because there are multiple relay proteins that can bind to the RTKs, multiple responses can be signaled at once. 9.Once a receptor tyrosine kinase is fully activated, what are the “typical” intracellular events that follow? Once the RTKs are active, the complexes dimerize and crossphosphorylate leading to a kinase cascade via specific activated relay proteins. 10. How are the kinases in a signal transduction cascade typically activated and deactivated? How is it an advantage to have a multistep kinase pathway? Kinase cascades are activated by secondary messengers or the phosphorylation of RTKs. They are deactivated through negative feedback loops that inhibit a kinase up the chain. It is an advantage to have multistep kinase pathways because more steps allows for more points of regulation. There are multiple steps along the pathway that can be inhibited by other chemical signals that the cell may use to regulate the cellular responses created by the pathways. Also, more steps create amplification of the signals being created. As an enzyme activates another the signal becomes greater until if finally activates a cellular response. 11. How might the IP gat3 Ca channel on smooth ER be considered functionally similar to the acetylcholine receptor? These channels are the same in that both the gated Ca2+ channel and the Ach receptor are ion channels that require a messenger to bind to it and allow a flow of ions down their gradient. These act as secondary messengers to trigger a response of the cell. 12. Describe two ways in which signal transduction can be terminated at the level of the receptor. Signal transduction can be terminated at the receptor level via receptormediated endocytosis which is when the receptor actually dislodges from the membrane and moves into the cytoplasm so it does not receive anymore ligand signals. Another way the signal can be terminated is by a competitive inhibitor binding preventing the receptor from receiving a signal. 13. What types of cells/organisms reproduce by binary fission? What types of cells/organisms reproduce by mitosis? What advantage(s) does mitotic cell division offer over binary fission? Single celled asexual reproducing organisms reproduce using binary fission. This is simple division for simple organisms such as prokaryotes because they have 1 circular DNA (chromosome) and no internal compartmentalization (no organelles) Multicelled asexual reproducing organisms reproduce using mitosis to produce genetically identical daughter cells. The advantage of mitosis over binary fission is that this division creates more opportunity for genetic diversity and that daughter cells inherit mother cell DNA which may include adaptations and beneficial mutations. 15. Distinguish between the general cellular events/processes occurring in interphase versus mitosis (i.e. what’s the cell “doing” while in interphase, what’s it doing in mitosis?) During interphase the cell goes through 3 phases: o G1 is when the cell is growing, synthesizing proteins, performing glycolysis and its specialized function (muscle tissue cell, liver cell, etc.) o S phase is when the cell is performing DNA replication to create homologs of chromosomes o G2 there is more cell growth, organelles are duplicated and DNA repair occurs to prepare for mitosis Mitotic phase is active cell division in which the cell goes through many different stages to divide the genetic material and the cell itself. 16. During what stage(s) of the cell cycle/mitosis is the highly condensed 1400nm chromosome structure present? What is the advantage to the cell in having the DNA in this form at this time? The DNA of the cell is condensed during prophase/prometaphase in order to keep all the important genetic information in a package so none is lost when it is divided. 17. Define the structural and functional relationship(s) between the kinetochore, the centromere, kinetochore microtubules and motor proteins during mitosis. The centromere region is where the chromatids are held tightly together and the kinetochore, a complex of proteins, is assembled. The kinetochore is where the microtubules interact when protruding from centrosomes—the microtubule organizing centers. Motor proteins on the microtubules walk, pulling the attached microtubules causing the chromatids to align at the equator of the cell during metaphase and eventually split at anaphase. 18. What key events occur in metaphase? What is the advantage to the cell in having those events occur? During metaphase the sister chromatids align at the equator of the cell and the microtubules are pulled taught by motor proteins. This event is important so that the sister chromatids can separate equally and equal amounts of genetic information can be split on to both sides of the cell during anaphase so when the cell splits during cytokinesis, the two daughter cells have identical information. 19. Define the event(s) occurring at the mitotic (metaphase) checkpoint. What is the cell “checking” for? What is the advantage to the cell in having this checkpoint present, or conversely, what major disadvantage would there be in NOT having this checkpoint present? During metaphase, the spindle assembly checkpoint occurs which checks to see if there is equal tension present of the microtubules on the sister chromatids. When this occurs the CDC20 protein releases from the kinetochore which acts as an allosteric activator to the anaphase promoting complex. The APC is an enzyme called ubiquitin ligase which gets added to a protein target and the protein is transported to a proteasome for degradation. o These proteins are securins which normally inhibit separases when not activated by Ub, which in turn, cleave cohesin proteins holding sister chromatids together. o Other proteins activated by Ub is cyclin, which, when its sent to degradation, the Cdk complexes present in S and G2 phase are inactivated causing the reversal of prophase which is telophase. 20. Why are cyclins called cyclins? Why are cdks called cdks? Define the general roles of cyclins and cdks in the regulation of progression through the cell cycle. Cyclins are proteins that are present throughout the cell cycle and they get their name from their cyclically fluctuating concentration in the cell. The concentration increases from G1 to Mitosis a and then it drastically decreases. CDKs are cyclindependent kinases. These are enzymes that add phosphate groups to proteins so long as cyclin is present and bound. CDKs act as the checkpoint regulators throughout the cell cycle. In order to be activated they need the allosteric activation from cyclin and the correct phosphorylation pattern. The CDKs phosphorylate condensins (DNA compaction), nuclear lamina (fragmentation of nuclear envelope), and the microtubule associated proteins (spindle formation). 21. What is cdc25? What enzymatic activity is associated with this protein? At what stage(s) of the cell cycle is this enzyme activated? In response to what cellular event? What role does cdc25 play in the G2 to M transition? CDC25 is a phosphatase enzyme that removes a phosphate group from an inactive cyclin CDK complex in order to activate it and push the cell from G2 into mitosis (prophase). CDC 25 is inhibited until DNA is done replicating as a checkpoint. 22. What is wee1? What enzymatic activity is associated with this protein? At what stage(s) of the cell cycle is this enzyme activated? In response to what cellular event(s)? What role does wee1 play in the G2 to M transition? Wee1 is a kinase that adds a phosphate to an inactive CDK before CAK kinase adds a second phosphate to the cyclinCDK complex and then CDC25 removes the phosphate that Wee1 originally. Wee1 can also regulate the process by adding back a phosphate group and keep the cyclinCDK complex inactive until DNA repair and cell growth is complete and ready for cell division. 23. Define the specific role played by the mitotic cyclin/cdk complex (AKA Mitosis Promoting Factor, MPF) in regulating progression through the cell cycle. What are its enzymatic targets? How does MPF achieve full activation of its kinase activity? MPF is the cyclinCDK complex that was discovered first and its concentration corresponds to that of cyclin. The MPF phosphorylates a variety of proteins initiating mitosis. It acts directly as a kinase and activates other kinases. It causes phosphorylation of various proteins of the nuclear lamina which promotes fragmentation of the nuclear envelope during prometaphase of mitosis. During anaphase, MPF helps switch itself off by initiating a process that leads to the destruction of its own cyclin. The noncyclin part of MPF, the CDK, persists in the cell, inactive until it becomes part of MPF again by associating with new cyclin molecules synthesized during the S and G2 phases of the next round of the cycle. 24. In general terms, how does the cell “know” when all kinetochores are attached to the correct microtubule organizing center? What is the nature of the signal sent from the kinetochore (i.e. is it a stop signal or a go signal?) What is the advantage to the cell in having the signal in this form? The cell knows when all kinetochores are attached to the correct centromere when motor proteins start to create tension and this tension is equal for all chromatids. CDC20 protein is released from the kinetochore and Ub targets specific proteins. This is a goahead signal during metaphase triggered by the release of separases that cleaves cohesins to allow the sister chromatids to separate. This is important to ensure daughter cells do not end up with missing or extra chromosomes. 25. What is the Anaphase Promoting Complex (APC)? What enzymatic activity is associated with this protein complex? When is APC activated? In response to what signal? What role does the APC play in the metaphase/anaphase transition, and in the exit of the cell from mitosis? APC is an enzyme known as Ubiquitin ligase that targets certain proteins to act as goahead signal at certain checkpoints during anaphase. APC is active allosterically when CDC20 is released from the kinetochore during anaphase. The Ub targets securins that had inhibited separases. When it binds to securins, the securins are sent to proteasomes to be degraded and this allows separases to cleave cohesin proteins which held sister chromatids together. Ub also targets cyclin to cleave it from cyclinCDK complexes forcing the cell to reverse prophase which is essentially telophase. 26. Consider the following statement: “Normal cells obey strict rules. Divide only when told. Die rather than misbehave” (Dr. Andrew Murray). How is this statement an accurate assessment of the cell division regulation normally observed in multicellular organisms? This statement describes the checkpoints throughout the cell cycle and the cells strict adherence to these before continuing to the next phase of the cycle. If the cell does move to the next phase before it has completed the goahead signal the cell will move to apoptosis which is programmed “clean” cell death. 27. Define the nature of the three main cell cycle checkpoints we discussed: G1 to S, G2 to M and Metaphase. What is the cell “checking”? G1S is where the cell “asks” permission to divide via RTK growth factors which are proteins that stimulate other cells to divide. G2M is where the cell checks to see if all DNA has been replicated and, if necessary, repaired. It is also checking to make sure the cell is big enough and that all the organelles have duplicated. Spindle Assembly is used to ensure all sister chromatid kinetochores are attached to microtubules and equal tension is created by motor proteins. 28. In addition to the three cell cycle checkpoints described above, the cell monitors irreparable DNA damage throughout the cell cycle. At the cellular/molecular level, explain the advantage to the multicellular organism of monitoring DNA damage and repair continuously, rather than simply at discrete cell cycle progression checkpoints. What happens in a cell that detects irreparable DNA damage? The advantage of detecting DNA damage throughout the cell cycle to be repaired is to ensure that the cell can continue to perform any specialized functions it has as well as translating RNA to transcribe for proteins that are needed to perform specialized function and eventually divide. A cell that detects irreparable DNA enters apoptosis to destroy itself so its incomplete or damaged DNA (if irreparable) is not passed on. 29. Define what is meant by density dependent inhibition and anchorage dependence in the context of the multicellular organism. What is the nature of this regulation at the molecular/cellular level? Density or Contact inhibition is regulated by growth factor signaling that prevents the cell from dividing anymore if there is “no room.” Essentially, once the voids of damaged or missing cells has been filled, the cells are signaled to not divide anymore. Anchorage Dependence means that in order to divide, cells must be attached to a substratum such as the extracellular matrix of a tissue. The signal to divide is signaled to the cell from plasma membrane proteins and elements of the cytoskeleton. 30. Define how loss of appropriate cell division/cell cycle regulation at the checkpoints or other growth control process leads to cancer and metastasis. Cancer cells do not heed the normal signals that regulate the cell cycle. Cancer cells do not need growth factors to grow and divide, instead, they may make the growth factor themselves, or they may have an abnormality in the signaling pathway that conveys the growth factors signal to the cell cycle control system. The DNA in a cell with undergo a mutation and is usually targeted by the body and destroyed (identified as nonself), however, if it avoids destruction, the cell can divide. If the cell has been transformed it will continue to divide beyond the normal 3050 times. If the cancer cell continues to divide and remain in one spot it will be referred to as a benign tumor. IF the cell has the genetics and ability to spread to new tissues and impair the functions of one or more organs the tumor is referred to as malignant. The cancer cells can lose attachment to neighboring cells and the extracellular matrix and they can enter the lymph system and blood stream and be transported to new parts of the body in a process called metastasis. 31. Why is it true that multiple mutations, affecting multiple growth control mechanisms, must occur in order for cells to become cancerous? Cells must first mutate to indefinitely reproduce as well as a mutation in DNA that may cause the transcription of proteins, specifically cell surface receptors to be “incorrect.” The cell may also mutate to be able to spread to new tissues causing a malignant tumor. The cell can be mutated to fail in its ability to metabolize. The cell with mutated cell surface receptors may also cause its attachment to other cells and the cytoskeleton to fail and enter lymph and blood vessels to cause metastasis. Finally, cells may even mutate to secrete signaling molecules that cause blood vessels to grow toward the tumor making metastasis easier. 32. What is meant by the “twofold cost of sex (or males)”? What short term and long term advantages and disadvantages are associated with asexual and sexual modes of reproduction? The twofold cost of sex refers to the theory that an asexual mutant may arise in a sexual population, half of which comprises males that cannot, themselves, produce offspring. With femaleonly offspring, the asexual lineage doubles it population in each generation. In reference to this, the disadvantages of sexual reproduction are that males and females must seek each other out to reproduce and that offspring only receive 50% genetic information from each parent. The advantage of sexual reproduction is increased chance of mutation and adaptation to environment because of the meiotic process to rearrange genes. The disadvantages of asexual reproduction are that the progeny are exact clones of the parents decreasing chance of genetic variation and mutation. This limits their ability to adapt to the environment and gain advantage over things that may kill it such as disease or other organisms. An advantage of asexual reproduction is the ability to produce more progeny at a faster rate to keep a population high and alive. 33. Distinguish between the terms haploid and diploid, then define the necessity for meiotic cell division in sexually reproducing organisms in that context. The pairs of homologous chromosomes in each human somatic cell is a consequence of our sexual origins. We inherit one chromosome of a pair form each parent. Thus, the 46 chromosomes in our somatic cells are actually two sets of 23 chromosomes. The number of chromosomes in a single set is represented by n. Any cell with two chromosome sets is called a diploid cell and has a diploid number of chromosomes, abbreviated 2n. For humans the diploid number is 46 (2n=46). In a cell in which DNA synthesis has occurred, all the chromosomes are duplicated, and therefore each consists of two identical sister chromatids, associated closely at the centromere and along the arms. Even though the chromosomes are duplicated we say the cell is diploid because it has only two sets of information. Unlike somatic cells, gametes contain a single set of chromosomes and are referred to as haploid cells. Each has a haploid number of chromosomes (n). The haploid number for humans is 23 (n=23). The set of 23 consists of the 22 autosomes plus a single sex chromosome: an unfertilized egg contains an X and sperm may contain an X or a Y. Sexually reproducing organisms use meiotic cell division because each germ cell contains 46 chromosomes. These germ cells divide mitotically and then have 92 chromosomes and then perform meiosis as reductive division twice to get to the haploid number of 23. A sperm and egg each have 23 chromosomes so when they combine, it creates a zygote with the diploid number of 46. 34. What important difference is observed between the molecular events of mitotic prophase and meiotic prophase I? How is it logical that this difference must exist, given the different physiological roles of mitotic and meiotic cell division? The important difference in mitosis prophase and meiosis prophase 1 are the homologs forming tetrads during synapsis. This is a structure of four chromosomes all held together by “zipperlike” proteins while the sister chromatids are also held together by cohesins (same as mitosis). The other major difference is that during prophase 1 in meiosis, recombination or crossing over occurs at the chiasmata. This is where molecules of non sister chromatids switch around to move alleles to the other homologs. The difference must exist because mitosis creates identical copies of cells and maintains the diploid number in every cell along with all of the genetic information. In meiosis the number of chromosomes must be reduced but after DNA is recombined to create variation either through reciprocal or nonreciprocal recombination. 35. Why is recombination referred to as an obligatory event during meiotic division? What advantage is offered to a species characterized by obligatory recombination during gamete formation? Recombination is obligatory because chromosomes are independently assorted during meiosis and humans produce a collection of gametes differing greatly in their combinations of the chromosomes inherited from parents. Crossingover produces recombinant chromosomes which carry genes derived form two different parents. In humans, an average of one to three crossover events occurs per chromosome pair, depending on the size of the chromosomes and the position of the centromeres. The advantage of recombination is the unlimited possibilities of genetic variation that can occur to create mutations which are the original source of different alleles. Sexual reproduction and the recombination of alleles creates diversity to help these organisms adapt to their environment. 36. Distinguish between the terms somatic cell and germ cell as they relate to humans. When during the human life cycle are they present/produced? Distinguish between the terms autosome and sex chromosome as they relate to humans. Why are sex chromosomes referred to as such? What is their relationship to “sex” in humans? Somatic cells are any and all cells through the body that make up tissues, muscles, organs, etc. Germ cells are specialized cells that perform meiosis to create gametes (Sperm and ova) in humans. They appear in the gonads of humans which in men are the testes and in women are the ovaries. Autosome are chromosomes that contain the genetic information (DNA) for everything except rd the genes for determining sex. Sex chromosomes are referred to as the 23 chromosome and are called this because they determine sex. Women have an X from their mother and an X from their father. Men have an X from their mother and a Y from their father. 37. What is the relationship between the following cellular events or structures: tetrad, chiasmata, homologous chromosomes, synapsis, recombination? Homologous chromosomes (homologs) come together in pairs to form tetrads in a process called synapsis. Once the four chromatids (2 pairs of sister chromatids) come together they can crossover each other in a process called recombination at chiasmata—regions where crossing over occurs. 38. What is meant by the terms nonreciprocal recombination and nonhomologous recombination? What is the consequence of such events at the level of the DNA? What potential consequences occur at the level of the cell? At the level of the human organism? Nonreciprocal recombination is when homologs do not recombine equally because of different break points at the chromatids. (ie 4 genes from one switch with only 3 genes on another chromatid). This can lead to the deletion of genes on one chromatid and the duplication of genes on the other. o This could lead to increased diversity, however, if the duplicated gene acts as a “backup” and can be mutated. This mutation could lead to diversity or adaptation in a human because the mutated gene could be transl
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