The effect of aromatic CoA esters on fatty acid synthetase: biosynthesis of omega-phenyl fatty acids.

Aromatic carboxylic acids ingested by, or formed in, the body can be converted to the CoA derivatives but the possible metabolic fate of these thioesters has not been investigated extensively. We have examined the effects of two such thioesters, benzoyl-CoA and phenylacetyl-CoA, on the mammalian fatty acid synthetase. Benzoyl-CoA inhibited the enzyme, apparently by competing with acetyl-CoA and malonyl-CoA for substrate binding sites. Phenylacetyl-CoA, on the other hand, could replace acetyl-CoA as a primer for the fatty acid synthetase reaction; the product was almost exclusively omega-phenyldodecanoic acid. The Km of the synthetase for phenylacetyl-CoA was considerably higher than that for acetyl-CoA and the rate of synthesis of omega-phenyldodecanoic acid was only 16% of that of palmitic acid. Experiments in which the rate of synthesis and release of omega-phenyl moieties from the synthetase was compared with that of n-aliphatic moieties indicated that the rate limiting step was the initiation of chain growth from phenylacetyl-CoA; release of the synthesized acyl moieties by chain terminating thioesterases was equally rapid in the case of omega-phenyl and n-aliphatic acids. Possible metabolic consequences of the effects of these aromatic CoA esters on lipogenesis are discussed.