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Pathway Description
Oxidation of Branched-Chain Fatty Acids
Homo sapiens
Metabolic Pathway
In the majority of organisms, fatty acid degradation occurs mostly through the beta-oxidation cycle. In plants, this cycle only happens in the peroxisome, while in mammals this cycle happens in both the peroxisomes and mitochondria. Unfortunately, traditional fatty acid oxidation does not work for branched-chain fatty acids, or fatty acids that do not have an even number of carbons, like the fatty acid phytanic acid, found in animal milk. This acid can not be oxidized through beta-oxidation, as problems arise when water is added at the branched beta-carbon. To be able to oxidize this fatty acid, the carbon is oxidized by oxygen, which removes the initial carboxyl group, which shortens the chain. Now lacking a methyl group, this chain can be beta-oxidized. Now moving to the mitochondria, there are four reactions that occur, and are repeated for each molecule of the fatty acid. Each time the cycle of these reactions is completed, the chain is relieved of two carbons, which are oxidized and are taken away by NADH and FADH2, energy carriers that collect the carbons energy. After beta-oxidation in the cycle of reactions, an acetyl-CoA unit is released and is recycled into the cycle of reactions in the mitochondria, until the chain is fully broken down into acetyl-CoA, and can enter the TCA cycle. Once in the TCA cycle, it is converted to NADH and FADH2, which in turn help move along mitochondrial ATP production. Acetyl-CoA also helps produce ketone bodies that are further converted to energy in the heart and the brain.
References
Oxidation of Branched-Chain Fatty Acids References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Lawson LD, Kummerow FA: beta-Oxidation of the coenzyme A esters of elaidic, oleic, and stearic acids and their full-cycle intermediates by rat heart mitochondria. Biochim Biophys Acta. 1979 May 25;573(2):245-54. doi: 10.1016/0005-2760(79)90058-4.
Pubmed: 444549
Yu W, Liang X, Ensenauer RE, Vockley J, Sweetman L, Schulz H: Leaky beta-oxidation of a trans-fatty acid: incomplete beta-oxidation of elaidic acid is due to the accumulation of 5-trans-tetradecenoyl-CoA and its hydrolysis and conversion to 5-trans-tetradecenoylcarnitine in the matrix of rat mitochondria. J Biol Chem. 2004 Dec 10;279(50):52160-7. doi: 10.1074/jbc.M409640200. Epub 2004 Oct 4.
Pubmed: 15466478
Wanders RJ, Vreken P, den Boer ME, Wijburg FA, van Gennip AH, IJlst L: Disorders of mitochondrial fatty acyl-CoA beta-oxidation. J Inherit Metab Dis. 1999 Jun;22(4):442-87.
Pubmed: 10407780
Zammit VA: The malonyl-CoA-long-chain acyl-CoA axis in the maintenance of mammalian cell function. Biochem J. 1999 Nov 1;343 Pt 3:505-15.
Pubmed: 10527927
Muoio DM, Seefeld K, Witters LA, Coleman RA: AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target. Biochem J. 1999 Mar 15;338 ( Pt 3):783-91.
Pubmed: 10051453
Watkins PA, Howard AE, Gould SJ, Avigan J, Mihalik SJ: Phytanic acid activation in rat liver peroxisomes is catalyzed by long-chain acyl-CoA synthetase. J Lipid Res. 1996 Nov;37(11):2288-95.
Pubmed: 8978480
Westin MA, Hunt MC, Alexson SE: Peroxisomes contain a specific phytanoyl-CoA/pristanoyl-CoA thioesterase acting as a novel auxiliary enzyme in alpha- and beta-oxidation of methyl-branched fatty acids in mouse. J Biol Chem. 2007 Sep 14;282(37):26707-16. doi: 10.1074/jbc.M703718200. Epub 2007 Jul 5.
Pubmed: 17613526,
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