Source and Transport of Acetyl-CoA

Acetyl-CoA is synthesized in mitochondria by a number of reactions oxidative decarboxylation of pyruvate, catabolism of some amino acids (e.g., phenylalanine, tyrosine, leucine, lysine, and tryptophan see Chapter 17), and 6-oxidation of fatty acids (see above). Since acetyl-CoA cannot be transported directly across the inner 

Transport dependent upon carnitine Carnitine participates in the transport of long-chain acyl-CoA into the mitochondria and plays a similar role in the transport of acetyl-CoA out of mitochondria. However, carnitine acetyl transferases have a minor role in acetyl-CoA transport. 

citrate not only modulates the rate of fatty acid synthesis but also provides carbon atoms for the synthesis. The oxaloacetate formed from pyruvate may eventually be converted (via malate) to glucose by the gluconeogenic pathway. The glucose oxidized via the pentose phosphate pathway augments fatty acid synthesis by providing NADPH. Pyruvate generated from oxaloacetate can enter mitochondria and be converted to oxaloacetate, which is required for the formation of citrate. 

Cytoplasmic generation of acetyl-CoA via citrate transport and related reactions. PPP = Pentose phosphate pathway FAS = fatty acid synthase. — - Negative allosteric modifier. — - Positive allosteric modifier. 

As a result, acetyl-CoA carboxylase and citrate synthase are inhibited. The stimulatory effect of prolactin is confined to the mammary gland and may involve synthesis of the enzyme. 

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