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Unformatted text preview: Pyruvate Dehydrogenase and Citrate Cycle Practice Problems Reading Chapter 17 End of the chapter questions End of chapter (499-501): 5, 6, 9, 15 (focus on part a and d) Then try these: What are the advantages of using a multisubunit complex (i.e. the pyruvate dehydrogenase complex) to catalyze the conversion of pyruvate to acetyl CoA? Substrate channeling by multisubunit complexes allows more efficient catalysis. The product of the 1st reaction becomes the substrate for the next reaction. In a multisubunit complex the product can be "passed off" to the next enzyme, whereas in a pathway composed of separate enzymes in solution (e.g. glycolysis) each product must diffuse to the next enzyme in the pathway. The conversion of malate to oxaloacetate in reaction 8 of the citrate cycle has a G = + 29.7 kJ/mol yet the reaction process from malate to oxaloacetate. Explain how this is possible. Oxaloacetate is rapidly consumed with each turn of the citrate cycle (and during gluconeogenesis) thus the reaction is continually pulled toward synthesis of oxaloacetate. The citrate cycle only operates under aerobic conditions even though O2 does not participate directly in any step in the cycle. Why is this so? O2 is the terminal electron acceptor for the electrons extracted during the citrate cycle. Without O2, then NADH and FADH2 generated during the redox steps of the citrate cycle would accumulate and there would be no available NAD+ or FAD to act as electron acceptors. Lipoic acid and FAD serve as catalytic coenzymes for the enzyme a-ketogluterate dehydrogenase (note typo correction). Based on your knowledge of the pyruvate dehydrogenase mechanism, propose a role for each of the coenzymes. Lipoic acid assists in the transfer of CoA to form succinyl CoA and FAD is involved in the redox reactions. The disease beriberi results from a lack of thiamin in the diet. What two metabolites would you expect to accumulate in individuals with beriberi after ingesting glucose. Pyruvate and lactate. Pyruvate accumulates because pyruvate dehydrogenase is less active, the excess pyruvate will be converted to lactate by lactate dehydrogenase. Explain why it makes sense that citrate inhibits the key glycolytic enzyme phosphofructokinase I. When citrate levels build up in the mitochondria it is transported to the cytoplasm, where glycolysis occurs. Thus increasing citrate concentrations links glycolysis to the citrate cycle. If citrate rises, then glycolysis stops as the citrate cycle will not be able to metabolize its products. When I was taking biochemistry as an undergraduate, succinyl-CoA synthase, which catalyzes the conversion of succinyl-CoA to succinate in a reaction that yields 1 molecule of GTP, was called succinate thiokinase. Why can this enzyme be classified as a kinase? It catalyzes the transfer of a phosphoryl group to GDP, thus forming GTP by substrate level phosphorylation. Kinases are enzymes that catalyze phosphorylation, so one could call this enzyme a kinase. Explain why plants must have an active glyoxylate pathway but this pathway is not necessary (and in fact not present) in animals. The glyoxylate cycle is crucial for seed germination. Seeds store energy in the form of fatty acids. During germination, the plant must use fatty acids as to generate carbohydrates through the glyoxylate cycle until it has sufficient photosynthetic cells and fix CO2 to make carbohydrates. As plants are autotrophs, there is not outside source of carbohydrate. Animals, on the other hand, are heterotrophs and can get carbohydrates from food. There is no need to convert fatty acids to carbohydrates. Why have some proposed to develop inhibitors of enzymes in the glyoxylate pathway as antimicrobial agents? What type pathogens might be susceptible to this type of inhibitor? Humans do not have a glyoxylate pathway, so if a pathogen needs this pathway it is a useful drug target. Microorganisms with long latency periods often require the glyoxylate pathway to survive in human tissues (or human cells) and could be susceptible to drugs that inhibit enzymes in the glyoxylate pathway. ...
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- Spring '07