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Pathway Description
Beta Oxidation of Very Long Chain Fatty Acids
Homo sapiens
Metabolic Pathway
The degradation of fatty acids occurs is many ways, but for the most part in most species it occurs mainly through the beta-oxidation cycle. Take mammals for example, in this subset of species we find that beta-oxidation takes place not only in mitochondria, but in peroxisomes as well. In contrast, it tends to be the case that in plants and fungi beta-oxidation is only seen in peroxisomes. The reason the beta-oxidation cycle is found to occur in both mitochondria and peroxisomes in mammals is thought to be that extremely long chain fatty acids will in fact undergo oxidation in both locations, an initial or first oxidation in peroxisomes and second oxidation in the mitochondria. There is however a difference between the oxidation cycle which occurs in both these organelles. Namely, that the oxidation undergone in peroxisomes does not have any coupling to ATP synthesis, unlike the corresponding oxidation which occurs in the mitochondria. We find rather that electrons are passed to molecules of oxygen, which produces hydrogen peroxide. Moreover, there is an enzyme which is found only peroxisomes which ties into this process. It can turn hydrogen peroxide back into water and oxygen and is catalase. To expound further the differences between the oxidation cycle found in the peroxisomes and the mitchondria consider the following three key differences. One, in the peroxisome the beta-oxidation cycle takes as a necessary input a special enzyme called, peroxisomal carnitine acyltransferase, which is needed to move an activated acyl group from outside the peroxisome to inside it. In mitochondrial oxidation similar but different enzymes are used called carnitine acyltransferase I and II. Difference number two is that oxidation in the peroxisome commences with catalysis induced by an enzyme called acyl CoA oxidase. Also, it should be noted that another enzyme called beta-ketothiolase which aids in peroxisomal beta-oxidation has a substrate specificity which differs from that of the mitochondrial beta-ketothiolase. Turning now to how the oxidation cycle function in mitochondria, note that the mitochondrial beta-oxidation pathway is composed of four repeating reactions that take place with each fatty acid molecule. The oxidation of fatty acid chains is a process of progress through repetition. With each turn of the cycle two carbons are removed from the fatty acid chain and the energy of the chemical bonds once housed by the molecule is captured by the reduced energy carriers NADH and FADH2. Acetyl-CoA is created in this 4 step reaction beta-oxidation process and is sent to the TCA cycle. Once inside the TCA cycle, the process of oxidation continues until even the acetyl-CoA is oxidized to CO2. More NADH and FADH2 result.
References
Beta Oxidation of Very Long Chain Fatty Acids References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Lodish, H. et al. Molecular cell biology. (2004) New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
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
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
Hunt MC, Solaas K, Kase BF, Alexson SE: Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism. J Biol Chem. 2002 Jan 11;277(2):1128-38. doi: 10.1074/jbc.M106458200. Epub 2001 Oct 22.
Pubmed: 11673457
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
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