Molecular Biochemistry II

Lipid Catabolism: Fatty Acids and Triacylglycerols

Reading:

Textbook Reading: Voet & Voet, Biochemistry, 3rd Edition, p. 914-921, 928-930, 940-942. Pages with related information: 382-385.

Some recent articles (optional reading): 
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.

Potential Test Questions:

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 of intermediates.
    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? 

Problem:

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.)

Copyright 1998-2007 by Joyce J. Diwan. All rights reserved.

Lecture Notes on
Lipid Catabolism

  Interactive Quiz on     
   Lipid Catabolism      

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