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Oxidation of Fatty Acids:- The ω Oxidation of Fatty Acids Occurs in the Endoplasmic Reticulum

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  p647-649

2026-06-13

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Oxidation of Fatty Acids:- The ω Oxidation of Fatty Acids Occurs in the Endoplasmic Reticulum

Although mitochondrial β oxidation, in which enzymes act at the carboxyl end of a fatty acid, is by far the most important catabolic fate for fatty acids in animal cells, there is another pathway in some species, including vertebrates, that involves oxidation of the ω (omega) car bon—the carbon most distant from the carboxyl group. The enzymes unique to ω oxidation are located (in vertebrates) in the endoplasmic reticulum of liver and kidney, and the preferred substrates are fatty acids of 10 or 12 carbon atoms. In mammal's oxidation is normally a minor pathway for fatty acid degradation, but when β oxidation is defective (because of mutation or a carnitine deficiency, for example) it becomes more important.

The first step introduces a hydroxyl group onto the ω carbon (Fig. 17–16). The oxygen for this group comes from molecular oxygen (O₂) in a complex reaction that involves cytochrome P450 and the electron donor NADPH. Reactions of this type are catalyzed by mixed function oxidases, described in Box 21–1. 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, and the molecule can enter the mitochondrion and undergo β oxidation by the normal route. In each pass through the β-oxidation pathway, the “double-ended” fatty acid yields dicarboxylic acids such as succinic acid, which can enter the citric acid cycle, and adipic acid (Fig. 17–16).

FIGURE 17–16 The oxidation of fatty acids in the endoplasmic reticulum. This alternative to β oxidation begins with oxidation of the carbon most distant from the α carbon—the (omega) carbon. The substrate is usually a medium-chain fatty acid; shown here is lauric acid (laurate). This pathway is generally not the major route for ox idative catabolism of fatty acids.

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