Metabolic Biochemisrty

• Outline and briefly describe the fate of proteins degraded in carnivores.
• What is a protease and why are they produced and secreted as zymogens?
• List the common characteristics of aminotransferases or transaminases.
• In humans, where do ingested proteins become broken down into respective amino acids?
• How are SGPT and SGOT (and creatine kinase) useful diagnostic enzymes?
• Describe the reaction catalyzed by glutamate dehydrogenase and briefly provide a rationale behind the direction of the allosteric control by ADP and GTP.
• PLP primarily plays a role as a coenzyme in the metabolism of molecules bearing amino groups. In what other metabolic reactions does it act as a coenzyme?
• Describe the roles of glutamine and glutamate in amino group metabolism and transport.
• Glutamate dehydrogenase works on glutamate in the liver. What two products does this reaction yield?
• How and under what circumstances does the kidney play a role in glutamine processing?
• List the four metabolites in the urea cycle that must cross the mitochondrial membrane.
• In the urea cycle, from where does aspartate get its amino group?
• Why is the urea cycle such an energy expensive process?
• What role does glutamate play in the central nervous system?
• Explain how the degradation of amino acids feeds into the central catabolic processes of the cell.
• List the amino acids that are degraded to α-ketoglutarate?
• a) List the amino acids ultimately converted to acetyl-coA.
  b) Tryptophan catabolism can yield acetyl-coA via two different pathways. List three other important biomolecules derived from intermediates of tryptophan breakdown.
• Which reaction pathway converts the carbon skeleton of alanine to a ketone body?
• How, specifically, is the branched-chain amino acid dehydrogenase complex regulated, and where may it be found?
• What is the fundamental difference between keto-genic amino acids and glucogenic amino acids?
• Organisms are constantly trying to achieve homeostasis, and the effects of amino acid oxidation and the production of
  urea are not limited to a single physiological system. Locate the following article and answer the questions below:
  Chan H, and Butterworth R. (2003) Neurochemistry International, 43 (4,5): 525-532.

  a) Increased brain ammonia leads to cerebral swelling via what mechanism?

  b) An increase in the presence of ammonia in the brain is often identified concomitant with increased extracellular concentrations of glutamate. T/F

• Select one of the disorders listed in table 18-2. Using information in your text and online, elaborate on the condition with respect to the specific defective enzyme (or complex) and process, relating them to the symptoms and effects.
• Read the following article and answer the associated questions:
  Townsend DM, Tew KD, and Tapiero H. (2004) Biomedicine and Pharmacotherapy, 58 (1): 47-55.

  a) In the conversion of dietary amino acid methionine to cysteine, a component of the antioxidant glutathione and precursor to taurine, what enzyme catalyzes the first step in this reaction?

  (Note that a deficiency of this enzyme leads to clinically recognized hypermethioninemia.)

  b) Birth defects have been associated with high levels of maternal homocysteine. How does administration of folic acid serve to protect the fetus?

1. Explain how the processes of oxidative phosphorylation and photophosphorylation are mechanistically similar.
2. Describe how the structure of mitochondria facilitates the physical separation of metabolic processes within a cell.
3. Compare the electron acceptors NAD+, NADP+, FMN and FAD and outline the number of hydrogen atoms and electrons that they carry.
4. What are the cellular roles of NADH and NADPH?
5. Outline the differences and similarities between cytochromes, iron sulfur proteins and flavoproteins as electron carriers.
6. What are the two components of the proton motive force in mitochondria?
7. Standard reduction potentials are used to predict the direction of redox reactions. Good electron donors have large positive E’o values. T/F
8. In reactions catalyzed by dehydrogenase, what role does coenzyme Q play?
9. Why are both F₁ and F_o necessary for the synthesis of ATP?
10. What is the general structure of the F_o F₁ ATP synthase system?
11. Which subunit(s) of the ATP synthase complex contain the catalytic site(s) for ATP synthesis?
12. How do inhibitors of electron transfer help to establish the order of the components in the electron transfer chain?
13. What is the difference between an oxidative phosphorylation uncoupler and an inhibitor?
14. Explain how the reducing equivalents of cytosolic NADH can become oxidized by the mitochondrial electron transfer
    chain, when NADH cannot cross the inner mitochondrial membrane.
15. What is the usual direction of flow of adenine nucleotides from the mitochondrial matrix to the cytosol and vice versa?
    How is this driven?
16. Briefly explain how the ratio of 2.5 ATP per NADH oxidized is derived.
17. What NADH shuttle is prevalent in liver, kidney and heart mitochondria?
18. Provide a brief overview of Mitchell’s chemiosmotic coupling model.
19. Describe the unique qualities of cyanobacteria with respect to energy production.
20. How does the structure of a chloroplast differ from that of a mitochondrion?
21. List the processes of photosynthesis that occur only in the presence of light and those that can occur in the absence of light.
22. Compare the structure of the chlorophyll molecule to the structure of the protoporphrin component of hemoglobin.
23. What are the ultimate electron donors and electron acceptors in chloroplasts and mitochondria?
24. What component of the proton motive force is most important in chloroplasts?
25. How are plants able to vary the ratio of NADPH and ATP formed in the light?

• How does the regulation of fructose 2,6 bisphosphate concentration differ in plants and animals?
• Starch synthesis in plants uses UDP-glucose instead of ADP-glucose (True or False).
• What is the net reaction, and stoichiometry, for each stage of the Calvin cycle?
• Explain in detail how the processes of fatty acid synthesis and fatty acid oxidation are similar and different.
• Describe the process of activation of acetyl-CoA for use in the synthesis of fatty acids and the role of the acyl carrier protein.
• What is the product of the condensation reaction in fatty acid synthesis, and what is the energy source that drives the reaction?
• What is the electron donor in the reduction of the carbonyl group? In the dehydration step, from where are the elements of water removed?
• What are the sources of acetyl CoA for fatty acid synthesis? What are the precursors of triacylglycerols?
• What is the acyl carrier in the elongation of palmitate? Compare/contrast the synthesis of palmitate versus the oxidation of palmitate.
• Describe the fatty acyl CoA desaturase reaction.
• Describe the process by which the drug ibuprofen reduces fever.
• Briefly describe triacylglycerol biosynthesis with respect to how it is regulated by insulin.
• What is the activating nucleotide triphosphate involved in glycerophospholipid metabolism? What common precursors do glycerophospholipids share with triacylglycerols.
• Outline the 4 steps in cholesterol synthesis. What enzyme catalyzes the committed step in cholesterol synthesis?
• Describe in detail the mechanisms controlling cholesterol synthesis.
• How are vitamins A, E, and K related to cholesterol biosynthesis?
• What are the general functions of mineralocorticoids and glucocorticoids?
• Why is HMG-CoA reductase a target in attempts to lower plasma cholesterol levels? Briefly explain how do lovastatin and cholestyramine work to lower blood cholesterol levels?
• The following article is a review of intracellular lipid particles. Read the portion relating to mammalian cells and answer the questions below.

  Zweytick D, Athenstaedt K, and Daum G. (2000) Biochimica et Biophysica Acta (BBA) ? Reviews on Biomembranes, 1469 (2): 100-120.

  • What major component of mammalian lipid particles is formed by esterification of cholesterol with long-chain fatty acids?
  • What role do perilipins play in regulating fatty acid synthesis?
  • How do we know that diacylglycerol acetyl transferase is not the sole enzyme capable of catalyzing a reaction using acyl CoA as a precursor to yield triacylglycerols?

• Search and locate the article entitled “Regulation of bile acid synthesis: pathways, nuclear receptors and mechanism” from the Journal of Hepatology authored by Chiang, Volume 40, Issue 3, March 2004, Pages 539-551 and answer the related questions.
• a.What are oxysterols, and what role do they play in cholesterol regulation?
• b.In the classic bile acid biosynthetic pathway what is the rate-limiting enzyme in the pathway, and where does this reaction take place?
• c.The classic pathway of bile acid biosynthesis is present in gall bladder cells and intestinal cells. T/F