Unit 1 1 UNIT 1 PART A: GLUCONEOGENESIS PART B: PYRUVATE DEHYDROGENASE AND THE TCA CYCLE PART A: GLUCONEOGENESIS Asignment: Nelson & Cox, pp. 551 - 558, 582 - 583, 585 - 588, 590, 918 - 919. 1. Gluconeogenesis a. What is meant by the term gluconeogenesis? Why is this proces important in animals? In what tisues does it mainly occur (p. 552)? b. Using Fig. 14-15 (p. 552) as a guide, name thre non-carbohydrate precursors of glucose. c. Why does gluconeogenesis require a pathway diferent than the reversal of glycolysis (p. 552)? 2. Glycolysis and Gluconeogenesis are opposing pathways (pp. 552 - 557). a. On Fig. 14-16 (p. 553) and Table 14-2 (p. 553), point out thre steps in glycolysis that are esentialy ireversible. Note that al the other reactions are reversible. Unit 1 2 b. Bypas 1: Conversion of pyruvate to phosphoenol pyruvate (Fig. 14- 17, p. 554) 1) Using structures, write balanced equations for the reactions involved. 2) Name the cofactor used by pyruvate carboxylase and describe its function (Fig. 14-18, p. 554 - you do not need to know the structure of biotin!). What is the role of ATP? 3) In this series of reactions, pyruvate is first carboxylated to oxaloacetate and then decarboxylated to phosphoenol pyruvate. Why is this series of steps important (p. 555)? 4) Use Fig. 14-19 (p. 555) to discuss two alternate pathways from pyruvate to phosphoenol pyruvate. c. Bypas 2: Conversion of fructose 1,6 bisphosphate to fructose 6- phosphate Write a balanced equation for the reaction catalyzed by fructose 1,6 bisphosphatase 1. Name the type of reaction (p. 556). d. Bypas 3: Conversion of glucose 6-phosphate to glucose Write a balanced equation for the reaction catalyzed by glucose 6- phosphatase. Name the type of reaction (p. 556). 3. The following summarizes the bioenergetics of glycolysis and gluconeogenesis. Net ATP glucose ? 2 pyruvate +2 2 pyruvate glucose - 6 a. Acount for the 6 ATPs required for gluconeogenesis. Remember that we are dealing with the conversion of two moles of pyruvate and that, energeticaly, ATP and GTP are equivalent. b. Which other step in gluconeogenesis can be described as an energy input? Unit 1 3 4. What is meant by a "futile cycle"? How are such cycles prevented (pp. 582 - 583)? 5. Use Fig. 15-15 (p. 586) to discuss the reciprocal regulation of phosphofructokinase 1 (glycolysis) and fructose 1,6-bisphosphatase (gluconeogenesis). Use Fig. 15-16 (p. 587) to discuss the role of fructose 2,6-bisphosphate? Use Fig. 15-17 (p. 588) to discuss how/when fructose 2,6-bisphosphate acumulates in cels. 6. Describe the reciprocal regulation of pyruvate dehydrogenase and pyruvate carboxylase (Fig. 15-20, p. 590). 7. The Cori Cycle: Use Fig. 23-20 (p. 919) to discuss the Cori cycle. PART B: THE PYRUVATE DEHYDROGENASE COMPLEX AND THE TCA CYCLE In Unit 10, you learned that glucose is converted to pyruvate by glycolysis in the cytosol. Pyruvate is transported through the mitochondrial inner membrane by a pyruvate transporter. An activated two carbon compound, acetyl CoA, is generated from pyruvate in the mitochondrion. Acetyl CoA then enters into the TCA cycle where large amounts of reducing power (energy) are generated in the form of NADH and FADH 2 . Asignment: Nelson & Cox, pp. 615 - 638. Since time does not permit study of the pyruvate dehydrogenase complex in as much detail as Nelson & Cox supplies, please read through the asignment and then go back to answer the objectives one by one. You are not required to learn the detailed mechanisms, but we want you to understand the role of each of the coenzymes involved. Unit 1 4 1. Oxidative decarboxylation of pyruvate to acetyl CoA (pp. 616 - 620) a. What is the name of the enzyme complex that forms acetyl CoA from pyruvate? (p. 616) b. Write the net reaction catalyzed by the pyruvate dehydrogenase complex. (Fig. 16-2, p. 616) c. How many coenzymes are involved in the conversion of pyruvate to acetyl CoA? Name them (p. 617). d. How many enzymes are involved in the conversion of pyruvate to acetyl CoA (p. 618)? e. Discuss "substrate channeling" (p. 619). What is the advantage of having these enzymes organized into a complex? f. Which coenzyme binds pyruvate and acomplishes the decarboxylation (Fig. 16-6, p. 619; se Fig. 14-14, p. 550, for a detailed structure)? g. Which coenzyme combines with the intermediate in "f" and acomplishes the oxidation step (Fig. 16-6, p. 619)? h. Draw the structure of acetyl lipoate (Fig. 16-6, p. 619). (Do not memorize the structure of lipoyl lysine!) i. What happens next to the acetyl group (Fig. 16-6, p. 619)? j. What are the functions of the other two cofactors (Fig. 16-6, p. 619)? Refering to Table 13-7 (p. 515), does it sem odd that FADH 2 is strong enough to reduce NAD + to NADH? Explain how this is possible (pp. 518 - 520). 2. The TCA cycle a. Using structural formulas, write the reaction catalyzed by citrate synthase to form citryl CoA and then citrate from Acetyl CoA and oxaloacetate (fig. 16-9, p. 623). How is the wasteful hydrolysis of acetyl CoA prevented (p. 622)? Unit 1 5 b. Using structural formulas, write the other reactions of the TCA cycle. Note what kind of reaction is occurring at each step. Use Fig. 16-7 (p. 621) as a guide for your work. Note that hydration, hydrolysis, and dehydrogenation have distinctly diferent meanings! c. Use Fig. 16-11 (p. 624) to discuss the mechanism of action of isocitrate dehydrogenase. d. Discuss the mechanism of coupling betwen high energy thioester cleavage and GTP synthesis by succinyl-CoA synthetase (Fig. 16-12, p. 626). 3. On your diagram, label the carboxyl carbon of citrate (a symmetrical molecule) which came from acetyl CoA (pink shading on Fig. 16-7, p. 621). Is this carbon randomized betwen the two ends of the molecule during the conversion of citrate to succinyl CoA? How can one explain the ability of an enzyme to distinguish betwen the two ends of a compound like citrate? (Box 16-3, p. 629) 4. Reduced coenzymes are generated in the TCA cycle (Fig. 16-13, p. 630) a. List the four oxidation reactions of the TCA cycle and tel which coenzyme picks up the electrons and H atoms released in each of these reactions? b. What eventualy happens to these electrons and H atoms? c. How many molecules of reduced coenzymes (identify them) are produced from one molecule of glucose? 5. In the cel, the TCA cycle is an important catabolic pathway. Name the thre clases of molecules that undergo their final oxidation in the TCA cycle (p. 631)? Unit 1 6 6. In the cel, the TCA cycle is an important anabolic pathway. a. Use Fig. 16-15 (p. 632) to ilustrate the anabolic function of the TCA cycle (do not worry about specific details of what is synthesized from which precursor). b. Write a balanced equation for the anaplerotic reaction catalyzed by pyruvate carboxylase (Table 16-2, p. 632) 1) Why is this reaction metabolicaly important (p. 631)? 2) Name the prosthetic group used by this enzyme and use Fig. 16-16 (p. 634) to describe its mechanism of action. 7. Discuss how the pyruvate dehydrogenase complex is regulated by both alosteric mechanisms and by covalent modification (pp. 635 - 636). 8. Control of the TCA cycle (pp. 636 - 637): a. Use Fig. 16-18 (p. 636) to discuss the other regulatory steps in the pathway. b. In what way does this inhibition or stimulation help a cel to balance its metabolic needs (pp. 636 - 637)? Jim Blankenship Microsoft Word - U11_F08.doc
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