Textbook Reading: Voet & Voet, Biochemistry, 3rd Edition, p. 914-921, 928-930, 940-942. Pages with related information: 382-385.
Some recent articles
T. Hajri & N. A. Abumrad (2002) "Fatty acid transport across membranes: Relevance to nutrition and metabolic pathology," Annu. Rev. Nutr. 22: 383-415.
P. Rinaldo, D. Matern & M. J. Bennett (2002) "Fatty acid oxidation disorders," Annu. Rev. Physiol. 64: 477-502.
J.-J. P. Kim & K. P. Battaile (2002) "Burning fat: the structural basis of fatty acid b-oxidation," Curr. Opinion in Struct. Biol. 12: 721-728.
D. G. Hardie & D. A. Pan (2002) "Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase," Biochem. Soc. Trans. 30: 1064-1070.
K. Bartlett & S. Eaton (2004) "Mitochondrial b-oxidation," Eur. J. Biochem. 271: 462-469.
D. Carling (2004) "The AMP-activated protein kinase cascade - a unifying system for energy control," Trends in Biochem. Sci. 29: 18-24.
D. Carling (2005) "AMP-activated protein kinase: balancing the scales," Biochimie 87: 87-91.
N. Gregersen, P. Bross & B. S. Andresen (2004) "Genetic defects in fatty acid b-oxidation and acyl-CoA dehydrogenases. Molecular pathogenesis and genotype-phenotype relationships," Eur. J. Biochem. 271: 470-482.
S.Y.-Yang, X.-Y.-He & H. Schulz (2005) "3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease," FEBS J. 272: 4874-4883.
B. Xue & B. B. Kahn (2006) "AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues," J. Physiol. 574: 73-83.
R. J. A. Wanders & H. R. Waterham (2006) "Peroxisomal disorders: The single peroxisomal enzyme deficiencies," Biochim. Biophys. Acta 1763: 1707-1720.
P. N. Black & C. C. DiRusso (2007) "Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and regulation," Biochim. Biophys Acta 1771: 286-298.
1. Write out the reaction sequence for one cycle of the mitochondrial pathway for b-oxidation of fatty acyl CoA, giving names and structures of intermediates (substrates and products of each reaction) and names of enzymes. Explain why this reaction sequence is called the "b-oxidation" pathway?
2. Write out the reaction catalyzed by Acyl-CoA Dehydrogenase, giving names and structures of reactant and product, and names of participating active site groups. What is thought to be the sequence of events during the reaction? What arrangement of active site groups in Acyl-CoA Dehydrogenase makes the reaction product stereospecific? How are electrons removed from the substrate transferred into the respiratory chain?
3. a. Diagram and describe the process by which the fatty acid moiety of
cytosolic fatty acyl-CoA is transferred into the mitochondrial matrix. Include
names of intermediates and enzymes, and structures of just the relevant portions
b. How is AMP-Activated Kinase involved in regulation of fatty acid oxidation? Explain the value to a cell of this regulation.
4. Name and draw the structure of any one ketone body that functions in metabolism. What is the role of ketone bodies, and where are they formed? Write out the reactions by which the ketone body you named is synthesized, giving names of reactants and products of each reaction (structures not required here). What conditions favor ketone body production, and why?
Catabolism of two 6-C glucose molecules through glycolysis, Krebs cycle, and oxidative phosphorylation yields approx. 60 ~P bonds of ATP (30/glucose). Compare the energy yield for oxidizing a 12-C fatty acid. (Note: Answers are in the Tutorial. Please do the problem before checking the tutorial.)
How many "high energy" (~) bonds are utilized in activating the fatty acid, by esterifying it to coenzyme A? (-)_________
How many times is the b-oxidation pathway repeated during oxidation of a 12-C fatty acid? _________
How many each of NADH______, FADH2______, and Acetyl CoA______ are produced, per 12-carbon fatty acid, in the b-oxidation pathway?
Oxidation of each acetyl CoA in Krebs cycle yields 3 NADH and one FADH2 (from succinate), resulting in additional production of _______NADH and _______FADH2.
Thus the yield is a total of _______NADH and _______FADH2.
In the respiratory chain, approx. 2.5 ~ bonds of ATP are produced per NADH and 1.5 ~ bonds of ATP per FADH2 (electrons entering the respiratory chain via coenzyme Q). Thus from reoxidation of NADH and FADH2 a total of _______ ~ bonds of ATP are produced per 12-C fatty acid.
Add to this the ~P bonds of GTP produced in Krebs Cycle (one GTP per acetyl-CoA) for a total of _______ ~P bonds produced.
Summing input and output yields a total of _______ ~P bonds per 12-C fatty acid oxidized. Does fat yield more energy than carbohydrate? _______
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