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Biosynthesis of Fatty Acids and Eicosanoids:- Acetate Is Shuttled out of Mitochondria as Citrate

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  p794-795

2026-06-29

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Biosynthesis of Fatty Acids and Eicosanoids:- Acetate Is Shuttled out of Mitochondria as Citrate

In nonphotosynthetic eukaryotes, nearly all the acetyl CoA used in fatty acid synthesis is formed in mitochondria from pyruvate oxidation and from the catabolism of the carbon skeletons of amino acids. Acetyl-CoA arising from the oxidation of fatty acids is not a significant source of acetyl-CoA for fatty acid biosynthesis in animals, because the two pathways are reciprocally reg ulated, as described below.

The mitochondrial inner membrane is impermeable to acetyl-CoA, so an indirect shuttle transfers acetyl group equivalents across the inner membrane (Fig. 21–10). Intramitochondrial acetyl-CoA first reacts with oxaloacetate to form citrate, in the citric acid cycle re action catalyzed by citrate synthase (see Fig. 16–7). Citrate then passes through the inner membrane on the citrate transporter. In the cytosol, citrate cleavage by citrate lyase regenerates acetyl-CoA in an ATP dependent reaction. Oxaloacetate cannot return to the mitochondrial matrix directly, as there is no oxaloacetate transporter. Instead, cytosolic malate dehydrogenase re duces the oxaloacetate to malate, which returns to the mitochondrial matrix on the malate–-ketoglutarate transporter in exchange for citrate. In the matrix, malate is reoxidized to oxaloacetate to complete the shuttle. Alternatively, the malate produced in the cytosol is used to generate cytosolic NADPH through the activity of malic enzyme (Fig. 21–9a).

FIGURE 21–9 Production of NADPH. Two routes to NADPH, cat alyzed by (a) malic enzyme and (b) the pentose phosphate pathway.