Metabolic Biochemistry / BIBC 102 First Exam / Spring 2004 I. (20 points) Fill in all of the enzyme catalyzed reactions which convert glycogen to lactate. Draw the correct structure for each intermediate molecule. (You do not need to give the correct name for each intermediate molecule or the correct name of the enzyme to receive full credit). Include the names or abbreviations of any other reactants and products (eg, ATP, ADP, Pi, NAD+, NADH, etc), and any required prosthetic groups (eg, biotin, TPP, etc.). Glycogen (draw the 2 terminal sugar subunits of the polymer only) lactate (draw structure)2 II. (15 points) When a muscle goes from rest to strenuous exertion, the primary source of ATP energy to drive muscle contraction is obtained from the conversion of glycogen to lactate. (A) Why is lactate produced from glycogen during strenuous exercise, not pyruvate or CO2? (B) Two key regulatory enzymes are largely responsible for the increased production of lactate from glycogen during strenuous exercise. What are these enzymes, and how are they activated by strenuous exercise? III. (10 points) Phosphonacetyl-L-aspartate (PALA) is a potent inhibitor of ATCase because it mimics the two physiological substrates of this enzyme. However, low concentrations of this unreactive bisubstrate analogue actually increase the reaction velocity. On addition of PALA, the reaction rate increases until an average of three PALA are bound per enzyme molecule (see graph below). This maximal velocity is 17-fold greater than in the absence of PALA. The reaction rate then decreases to nearly zero on adding three more molecules of PALA per enzyme. Why do low concentrations of PALA activate ATCase?3 IV. (20 points) Consider the reaction X → Y, a reaction for which ∆G°′ = +17 kJ/mol. A. What is the equilibrium constant for this reaction? (show your work!) Keq = [Y]/[X] = B. In a typical cell this reaction is coupled to the hydrolysis of ATP: X + ATP → Y + ADP + Pi Given that the ∆G°′ for ATP hydrolysis is –30.5 kJ/mol, what is ∆G°′ for the coupled reaction? (show your work!) ∆G°′ (coupled) = C. What is the equilibrium constant for the coupled reaction? (show your work!) Keq (coupled) = D. What is the expected ratio of [Y]/[X] in a cell in which the ratio of [ATP] to [ADP][Pi] is 5000? (show your work!) [Y]/[X] = E. What is the extent to which the hydrolysis of a single high energy bond in ATP increases the degree to which products are favored? (You must show your work for credit.) [Y]/[X] (coupled ATP hydrolysis) ________________________ = [Y]/[X] (no coupled ATP hydrolysis)4 V. (45 points) Multiple Choice. Choose only one answer for each question. 1. Which one of the following statements is most blatantly false? (A) Primary structure refers to the covalent structure of a protein (e.g., the amino acid sequence.) (B) Quaternary structure refers to the way in which subunits of a multi-subunit protein are packed together, and therefore is only found in proteins with more than one polypeptide chain. (C) The amino acids H and K are more likely to be found in the interior of a globular protein than the amino acids L and M. (D) In an α helix, all N-H groups of the peptide bond form hydrogen bonds with the C=O groups that are four residues apart in the amino acid sequence. (E) In an antiparallel β pleated structure, the R groups alternately project above and below the β sheet plane, and so define the character of the surfaces of the sheet. 2. Which one of the following statements is most blatantly false? (A) Km, the Michaelis constant, is the substrate concentration at which the reaction velocity, Vo, is half of Vmax, and the units of Km are therefore molar. (B) If an enzyme increases the rate constant for the conversion of substrate to product (kcat) by 108, it must also increase the rate constant for the conversion of product to substrate by 108. (C) Enzymes decrease ∆G‡, the activation free energy, for the reactions they catalyze by selectively stabilizing the transition state. (D) Competitive inhibitors bind reversibly to the active site of an enzyme and prevent binding of the substrate. (E) An enzyme obeying Michaelis Menten kinetics will achieve 1/3 of Vmax at a substrate concentration which is 1/3 Km. 3. Which one of the following statements is most blatantly false? (A) Allosteric regulation of enzyme activity requires that there be at least one additional site, distant from the active site, to which an allosteric effector can bind. (B) When an allosteric inhibitor binds to the allosteric site on an enzyme, it shifts the R/T equilibrium to the T state. (C) The phosphorylation of a specific serine residue in each subunit of glycogen phosphorylase activates the enzyme by shifting the R/T equilibrium to the R state. (D) Since phosphofructokinase shows a sigmoid dependence of Vo on [ATP], it must have more than one active site. (E) For an allosteric enzyme, the substrate concentration at which half maximal velocity is attained, called K0.5, will be greater if the conformation of the enzyme is in the R state than if it is in the T state. 4. Which one of the following statements is most blatantly false? (A) Phosphoglucomutase is required to convert glucose to pyruvate. (B) Glycogen phosphorylase b is allosterically activated by AMP. (C) Phosphofructokinase is allosterically activated by AMP and inhibited by ATP. (D) Pyruvate kinase is allosterically inhibited by ATP, acetyl CoA, and long chain fatty acids. (E) Glycolysis, glycogenolysis, and lactate formation occur in the cytosol of the cell, not in the mitochondria. 5. Which one of the following statements is most blatantly false? (A) At steady state in a typical cell, the reactions catalyzed by glyceraldehydes-3-phosphate dehydrogenase and 3-phosphoglycerate kinase are essentially at equilibrium. (B) Adenylate kinase catalyzes the reaction: AMP + ATP ⇄ 2 ADP5 (C) An increase in the phosphorylation potential (i.e., the [ATP]/[ADP][Pi] ratio) will increase the rate of an ATP-generating catabolic pathway. (D) For the phosphofructokinase reaction in a typical cell, the ratio of the reactants (fructose-6-phosphate and ATP; numerator) to products (fructose-1, 6-bisphosphate and ADP; denominator)
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