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While the main route of fatty acid metabolism is through beta-oxidation, some minor metabolic pathways such as omega oxidation also contribute to the metabolism of fatty acids and other molecules. Omega oxidation occurs in the endoplasmic reticulum rather than the mitochondria, the site of beta-oxidation. The omega carbon in a fatty acid is the carbon furthest in the alkyl chain from the carboxylic acid. In the omega oxidation pathway, this carbon is progressively oxidized first to an alcohol and then to a carboxylic acid, creating a molecule with a carboxylic acid on both ends. The first step in the pathway is catalyzed by a cytochrome P450 mixed function oxidase and requires both oxygen and NADPH. Oxidation of the alcohol is catalyzed by an alcohol dehydrogenase and aldehyde dehydrogenase catalyzes the formation of the dicarboxylic acid.If the initial substrate was a long chain fatty acid, then the resulting dicarboxylic acid can enter the beta-oxidation pathway to be shortened at both ends of the molecule at the same time. When beta-oxidation is complete, the product is short chain dicarboxylic acids like succinate or adipate. Succinate enters the Kreb's cycle, and adipate's presence in blood or urine can be monitored to determine the degree of omega oxidation in an individual. Other molecules in addition to fatty acids can also enter the omega oxidation pathway. Other molecules with long alkyl chains also enter omega oxidation, becoming more water-soluble as a result and more easily excreted from the body.Although omega oxidation is normally a minor pathway of fatty acid metabolism, failure of beta-oxidation to proceed normally can result in increased omega oxidation activity. A lack of carnitine or carnitine palmitoyltransferase activity (see Mitochondrial Carnitine Palmitoyltransferase pathway) prevents fatty acids from entering mitochondria can lead to an accumulation of fatty acids in the cell and increased omega oxidation activity.
Contributor: Glenn Croston, PhD.
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