Omega oxidation (ω-oxidation) of fatty acid • Omega oxidation (ω-oxidation) is a process of fatty acid metabolism in some species of animals. • It is an alternative pathway to beta oxidation that, instead of involving the β carbon, involves the oxidation of the ω carbon (the carbon most distant from the carboxyl group of the fatty acid). • The ω (omega)-carbon (the methyl carbon) of fatty acids is oxidized to a carboxyl group in the endoplasmic reticulum. • The process is normally a minor catabolic pathway for medium-chain fatty acids (10-12 carbon atoms), but becomes more important when β oxidation is defective (because of mutation or a carnitine deficiency, for example).

Location

In vertebrates, the enzymes for ω oxidation are located in the smooth ER of liver and kidney cells, instead of in the mitochondria as with β-oxidation. • Substrate: Medium to Long chain fatty acids (Fatty acid with 10-12 carbon atoms). • End Product: Dicarboxylic acids are produced.

Steps

• The first step introduces a hydroxyl group onto the ω-carbon.

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• The oxygen for this group comes from molecular oxygen (O 2) in a complex reaction that involves cytochrome P450 and the electron donor NADPH. • Reactions of this type are catalyzed by mixed function oxidases. • Two more enzymes now act on the ω carbon: • Alcohol dehydrogenase oxidizes the hydroxyl group to an aldehyde, and • Aldehyde dehydrogenase oxidizes the aldehyde group to a carboxylic acid, producing a fatty acid with a carboxyl group at each end. • At this point, either end can be attached to coenzyme A, or the molecule can enter the mitochondrion and undergo β-oxidation by the normal route. • In each pass through the oxidation pathway, the “double-ended” fatty acid yields dicarboxylic acids such as succinic acid, which can enter the citric acid cycle, and adipic acid.

Significance

• It is a subsidiary pathway for β-oxidation of fatty acids when β-oxidation is blocked. • It is observed that ω- and (ω-1)-oxidation of fatty acids are related to energy metabolism in some laboratory animals such as musk shrews and Mongolian gerbils. • Studies confirm that ω- and (ω-1)-oxidation of fatty acids play crucial roles in the production of insect pheromones of honeybees and in the formation of biopolyesters of higher plants. • Many studies also have demonstrated that the ω-oxidation serves to provide succinyl-CoA for the citric acid cycle and for gluconeogenesis under conditions of starvation and diabetes.

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