CHAPTER 20 Tricarboxylic Acid Cycle OBJECTIVES: 1. To understand or describe any pathway or cycle, start with the following paradigm for the TCA cycle. Names: Functions: Substrates: Products: Control Enzymes: Regulation: Compartment(s): Tissues of interest: 2. Name the four dehydrogenase enzymes of the TCA cycle. What are the substrates and products of each reaction? 3. What is the approximate energy yield from the oxidation of one acetyl CoA molecule? 4. Name the enzyme of the TCA cycle that catalyzes a substrate level phosphorylation. 5. What is the difference between a substrate level phosphorylation and oxidative phosphorylation? 6. Compare NADH and FADH with respect to: (1) Mechanism of accepting or donating electrons, (2) Affinity for the apoenzyme, (3) reactivity in solution, and (4) ability to act as a feedback inhibitor or activator. 7. What is the purpose of the thioester bond in acetyl CoA and succinyl CoA? 8. Name the five cofactors of the a-ketoglutarate dehydrogenase reaction. Name the vitamins from which four of them are derived! What is the advantage of a multienzyme complex? 9. Several enzyme reactions in the TCA cycle are considered irreversible. Why? 10. Given the delta-G0! for each enzymatic step in a sequence of enzymatic reactions, be able to state the delta-G0! for the overall reaction. 11. How is the rate of the TCA cycle linked to muscle contraction and the utilization of ATP? 12. Name two control enzymes of the TCA cycle. 13. Name four dietary sources of acetyl CoA! 14. Which enzyme reaction in the TCA cycle is similar to the pyruvate dehydrogenase reaction? How could this relationship come about? 15. Why are the symptoms for pyruvate dehydrogenase complex deficiency so apparent in the central nervous system and not in most other tissues? 16. Explain how the rate of the pyruvate dehydrogenase complex is related to the rate of utilization of ATP. 17. Explain how muscle contraction is related to the rate of the pyruvate dehydrogenase reaction. 18. Name five pathways which use TCA cycle intermediates as substrates. What is the effect of these pathways on the TCA cycle? 19. If TCA cycle intermediates are constantly being removed for biosynthesis, why doesn't the cycle stop? 20. Be able to fully describe the anaplerotic reaction that links glycolysis and the TCA cycle. Name the enzyme, substrate, product, biological compartment and tissues of interest. Name the regulatory factor (activator) and explain how the system regulates the production of the TCA cycle intermediate. What coenzyme is used in the reaction? 21. Why are the symptoms for pyruvate carboxylase deficiency so apparent in the central nervous system and not in most other tissues? 22. In addition to pyruvate, name two other classes of compounds that can be used to as substrates for anaplerotic reactions. 23. Concerning Otto Shape, can succinate be oxidized without oxygen being consumed? 24. Concerning Otto Shape, explain the effect of increased muscle contraction upon the concentrations of ATP, ADP, AMP, NADH, FAD(2H), and Acetyl Co A. What effect does this have upon the rate of the TCA cycle and the pyruvate dehydrogenase reaction? 25. Concerning Otto Shape, what effect does the increased calcium ion concentration in a contracting muscle have upon the rate of the TCA cycle and the pyruvate dehydrogenase reaction? 26. Concerning Otto Shape, most of the pyruvate produced during exercise was either oxidized to acetyl CoA or reduced to lactate. Why did training increase the amount of pyruvate being oxidized? 27. Concerning a patient who suffers from anorexia nervosa and may have developed subclinical deficiencies of many vitamins, which vitamins would you prescribe to be positive that the pyruvate dehydrogenase and the pyruvate carboxylase reactions would have an adequate amount of cofactors? 28. Concerning Al Martini who is an alcoholic, why does he have a thiamine deficiency? 29. Concerning Al Martini: Given that a-ketoacids build up in the heart in wet beriberi, develop a scenario that would explain why peripheral vessels dilate and cardiac muscles loose their contractility. 30. Understand the meaning of each of the keywords. KEYWORDS: acetoacetate, acetyl CoA, a-ketoacids, a-ketoglutarate, a-ketoglutarate dehydrogenase, amino acids, amino acid synthesis, ATP, ATP/ADP, Ca++, Citric Acid Cycle, CoASH, ethanol, FAD, FADH2, fatty acid, fatty acid synthesis, free radicals, fumarate, GDP, gluconeogenesis, GTP, heme synthesis, hydrogen atom, isocitrate, isocitrate dehydrogenase, Krebs Cycle, lipoate, malate, malate dehydrogenase, NADH, NADH/NAD+, neurotransmitter synthesis, niacin, oxaloacetate, pantothenic acid, phosphatase, prosthetic groups, pyruvate, pyruvate carboxylase, pyruvate dehydrogenase complex, pyruvate dehydrogenase kinase, riboflavin, semiquinone, substrate channeling, succinate, succinate dehydrogenase, succinyl CoA, succinyl CoA synthetase, succinate dehydrogenase, succinate thiokinase, TCA cycle, thiamin, thiamine-PP, thioester bond.. ASSIGNMENTS: Examine questions in chapter 20 text except Q: on page 367. Work questions 1, 2, 3, 4, and 5 at the end of Chapter 20 Understand the meaning of the key words in the context of Chapter 20 Practice Questions for Chapter 20 Objectives No Other Help REFERENCE: Marks' Basic Medical Biochemistry: A Clinical Approach, 2nd Edition, 2004, Williams and Wilkins (ISBN: 0-7817-2145-8) by Colleen M. Smith PhD, Allan D. Marks MD, and Michael A. Lieberman PhD