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Oxidation of Fatty Acids:- Fatty Acid Oxidation Is Tightly Regulated

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  p642-643

2026-06-13

93

Oxidation of Fatty Acids:- Fatty Acid Oxidation Is Tightly Regulated

Oxidation of fatty acids consumes a precious fuel, and it is regulated so as to occur only when the need for en ergy requires it. In the liver, fatty acyl–CoA formed in the cytosol has two major pathways open to it: (1) β-oxidation by enzymes in mitochondria or (2) conversion into triacylglycerols and phospholipids by enzymes in the cytosol. The pathway taken depends on the rate of transfer of long-chain fatty acyl–CoA into mitochondria. The three-step process (carnitine shuttle) by which fatty acyl groups are carried from cytosolic fatty acyl–CoA into the mitochondrial matrix (Fig. 17–6) is rate-limiting for fatty acid oxidation and is an important point of regulation. Once fatty acyl groups have entered the mitochondrion, they are committed to oxidation to acetyl-CoA.

Malonyl-CoA, the first intermediate in the cytosolic biosynthesis of long-chain fatty acids from acetyl-CoA (see Fig. 21–1), increases in concentration whenever the animal is well supplied with carbohydrate; excess glucose that cannot be oxidized or stored as glycogen is converted in the cytosol into fatty acids for storage as triacylglycerol. The inhibition of carnitine acyltransferase I by malonyl-CoA ensures that the oxidation of fatty acids is inhibited whenever the liver is amply sup plied with glucose as fuel and is actively making triacylglycerols from excess glucose.

Two of the enzymes of β oxidation are also regulated by metabolites that signal energy sufficiency. When the [NADH]/[NAD⁺] ratio is high, -hydroxyacyl CoA dehydrogenase is inhibited; in addition, high concentrations of acetyl-CoA inhibit thiolase (Fig. 17–12).