This biochemistry assignment is pretty hard!! If someone who is good at biochemistry can help me I would be grateful. There are 39 questions and most of them are multiple choice.Can you help?
Unit 3 Study Guide ____ 1. A “good enzyme” (i.e. higher catalytic power for a given chemical reaction) will bind with the highest affinity to which of the following? 2 pts a. The substrate(s). b. The transition state. c. The product. ____2. Explain why most enzymes are relatively large compared to the size of their substrate binding site(s) and how this enables them to be the most powerful chemical catalysts known (i.e. several orders of magnitude more efficient than inorganic catalysts). For full credit, your answer should be at least 3-4 sentences long and discuss non-covalent and/or covalent interactions made between the substrate, transition state, and/or product. 4 pts ____ 3. You are studying different mutations in an enzyme that is important for photosynthesis that have been found in different species across planet Earth with different levels of sunlight. Which of the following enzymes has the highest catalytic efficiency? 2 pts a. Kcat = 4 * 10 7 s-1, Km =5M, Vmax = 1 mol/s b. Kcat = 4 * 10 7 s-1, Km =1M, Vmax = 1 mol/s c. Kcat = 4 * 10 7 s-1, Km =10M, Vmax = 5 mol/s d. Kcat = 4 * 10 7 s-1, Km =10M, Vmax = 20 mol/s e. Kcat = 2 * 10 7 s-1, Km = 5M, Vmax = 20 mol/s Questions 4-6 refer to the free energy diagram showing progress of a reaction in the presence (blue line) or absence (black line) of an enzyme that is shown below. S= substrate, P = product. ____ 4. Covalent bonds made between the enzyme and substrate contribute are correlated changes in free energy in which part of the graph? 2 pts a. Arrow #1 b. Arrow #2 c. Option 3 d. Options 1 & 3. e. Options 2 & 3 ____ 5. Non-covalent bonds made between the enzyme and substrate are most likely to contribute to which thermodynamic change? 2 pts a. Option 1 b. Option 2 c. Option 3 d. Options 1 & 3. e. Options 2 & 3 Subtotal __/ 12 pts ____ 6. True or false. Regardless of the concentrations of substrate and product, the enzyme that catalyzes this chemical reaction will only increase the rate of the reaction in the forward direction (conversion of substrate into product). 2 pts A/ True B/ False ____ 7. A patient who has HIV was recently diagnosed with cancer. Taxol, a chemotherapeutic drug that stabilizes microtubules (preventing rapidly-dividing cancer cells from dividing), also binds to HIV protease and inhibits its activity. What side-effect would this drug have on the patient in terms of their HIV infection? 3 pts A/ Patient may exhibit worsening symptoms (progression of HIV -> AIDS) because without HIV protease the HIV proteins will not be cleaved and the virus will propagate uncontrollably. B/ Patient may exhibit worsening symptoms (progression of HIV -> AIDS) because without HIV protease the blood coagulation pathway is desensitized (i.e. turned off). C/ Patient will be helped (HIV inhibited) because the HIV proteins that are expressed polycistronically from its genome remain inactive unless cleaved by HIV protease. D/ Patient will be helped (HIV inhibited) because HIV depends on HIV protease to cleave antigens presented by killer T-cells of the immune system. E/ Patient will not be effected by this drug because HIV protease does not play a role in the HIV life-cycle. ____ 8. In 2-3 sentences, explain why it is important to determine Vo (initial velocity) during enzyme kinetic experiments conducted at steady state (as opposed to taking later time points). Include in your answer the key variable that changes in enzyme kinetic experiments at later time-points that complicates interpretations of kinetic interpretations of your enzyme’s function. 4 pts ____ 9. Lineweaver-burke plots are derived by taking which measurements from a kinetic experiment? 2 pts a/ pre-steady state b/ steady state ____ 10. Which type(s) of kinetic experiments can tell you about distinct steps in an enzyme’s mechanism? 2 pts a/ pre-steady state b/ steady state c/ both pre-steady state and steady state d/ neither pre-steady state nor steady state ____ 11. Acid-base catalysis (transfer of a proton) is the single-most common reaction in biochemistry and is often used as part of enzymes as a strategy to stabilize a charged intermediate that is part of reaction coordinate pathway. The best (i.e. most abundant) proton donor/acceptor is water, but this is often not available in the active site of an enzyme when substrate is bound. What part of an enzyme substitutes as a proton donor/acceptor? 2 pts a/ the alpha carbon b/ R-groups such as Glu or Lys c/ parts of the peptide backbone d/ R groups such as Leu or Pro e/ Options C and D Subtotal __/ 15 pts ____ 13. On average, which option takes the longest time-period to occur? 3 pts a/ dissociation of a transition state analog molecule from an enzyme after it has bound b/ the life-span of the transition state as substrate becomes product, or vice versa c/ completing this semester ? ___ 14. Which of the following options is/are correct regarding the mechanism of enolase and its catalysis of conversion of 2-phosphoglycerate to phosphoenolpyruvate. Mark all that apply. 3 pts a. Enolase utilizes two types of catalysis; (1) metal ion catalysis, which is mediated by 1-2 Mg2+ ions and general acid-base catalysis. b. A carboxyl group in the substrate, 2-phosphoglycerate, helps make a hydrogen atom that is covalently bound to carbon #2 of 2-phosphoglycerate more susceptible to leave; this is because it “steals” electrons away from carbon #2. These electrons are required for sharing with this hydrogen atom during formation of the covalent bond; by removing electron density from this region, the hydrogen atom is therefore more likely to leave. c. Mg2+ ions form ionic bonds (termed “coordination bonds”) with the carboxyl group of 2-phosphoglycerate; this has the effect of decreasing the electron pulling effect of the carboxyl group on the hydrogen atom of carbon #2 of 2-phosphoglycerate (i.e. raising its pKa value), making it even more likely to be removed. d. As the reaction progresses, an unstable enolate intermediate is formed. It is unstable because there are two negatively charged Oxygen atoms present on the carboxyl group of the substrate. e. Mg2+ play a 2nd role in enolase’s mechanism by “shielding” (stabilizing the charge) of the unstable intermediate. ____15. Earlier this semester, you spent some time looking at the structure of progerin, the mutant version of a protein called Lamin A that causes the most common form of Progeria (a premature aging syndrome). Due to a mutation, Progerin is permanently farnesylated, leading to to accumulation at the nuclear envelope. The name of the enzyme that adds the farnesyl group to progrein is farnesyl transferase. Lonafarnib is a drug that is being used to treat progeria, which we will discuss to end the semester. Lonafarnib is a farnesyl transferase inhibitor. Lonafarnib binds reversibly to the farnesyltransferase active site to prevent its interactions with substrate, such as progerin. Studies indicated that Lonafarnib cannot bind to farnesyltransferase when progerin is bound to the active site of farnesyltransferase. What type of inhibitor is lonafarnib? 2 pts a. Transition state analog b. Competitive inhibitor c. Noncompetitive inhibitor d. Uncompetitive inhibitor e. Mixed Inhibitor Subtotal __/ 8 pts ____16. You manage to express and purify farnesyltransferase and progerin and measure the initial velocities for conversion of progerin into farnesylated progerin by the enzymatic activities of farnesyl transferase in vitro. Which of the following graphs correctly describes the expected relationship, based on the type of inhibition you chose in the previous answer? . Select all that apply . Note: pay attention to the labels for X- and Y-axes. Some graphs line-weaver-burke ( double-reciprocal plots), others are not. 5 pts Subtotal __/ 5 pts Before Lonafarnib was used to treat Progeria, it was actually used to treat cancers in which Ras was mutated to be constitutively on. Based on what you know about GCPR signaling, suggest a mechanism by which Ras promotes cancer as well as how Lonafarnib prevents cancer cells that have mutations in the Ras gene from growing by answering the following questions. ____17. Which component of the GPCR signaling pathway is GPCR? 3 pts A/ GPCR B/ G protein C/ Effector protein D/ Catalyzes chemical reaction that facilitates conversion of cAMP to 5’-AMP. E/ GTPase activator protein (GAP) ____18. Mutations in Ras commonly occur in the p-loop. What would effect would this have? Mark all that apply. 3 pts A/ GTP in the cell can never bind to Ras B/ GTP in the cell can bind to Ras and Ras hydrolyzes GTP -> GDP more rapidly C/ GTP in the cell can bind to Ras and Ras never hydrolyzes GTP D/ Ras will cause signaling even in the absence of a signal E/ Ras will always associate with its effector protein ____19. What is the function of farnesylation in signaling? What, exactly, do you think Ras is unable to bind to anymore and interact with if it is not farnesylated (as a result of treating cells with lonafarnib)? Answer in 2-3 sentences, please. 4 pts Hint: in the cell, it is not enough to simply be active, you often have to localized to the right cellular compartment to work. ____20. βARK and β-arrestin modulate β-adrenergic receptor signaling using which of the following mechanisms? Mark all that apply. 3 pts A/ Desensitization and receptor (GPCR) endocytosis B/ Decreasing the concentration of extracellular ligand C/ Increasing GTPase activity of Gs,⍺ D/ Degrading cAMP, the secondary messenger. E/ Removing phosphate group of β-phosphorylase ____21. Which is/are true about the mechanism by which βARK and β-arrestin modulate β-adrenergic receptor signaling? Mark all that apply. 3 pts A/ After GTP binds to Gs,⍺, Gs,⍺ diffuses in the membrane and binds to β-arrestin B/ β-arrestin phosphorylates the cytoplasmic tail of β-adrenergic receptor C/ βARK binds phosphorylated β-adrenergic receptor, then directly binds a coat protein called clathrin D/ Clathrin helps promote endocytosis of β-adrenergic receptor E/ β-adrenergic receptor can be further sorted into the lumen of late endosomes, leading to the formation of multivesicular bodies (MVB’s). MVB’s can fuse with the lysosome, resulting in degradation of the receptor. Subtotal __/ 16 pts ____22. A novel inhibitor of Ras has been discovered. The inhibitor can bind reversibly to Ras and its affinity for Ras is the same in the presence or absence of GTP/GDP. The inhibitor is a _________. 3 pts A/ Competitive inhibitor B/ Uncompetitive inhibitor C/ Mixed inhibitor D/ Noncompetitive inhibitor E/ Transition state analog F/ Suicide inhibitor ____23. Another novel inhibitor