NONHOMOGENEOUS LABELING OF LIVER EXTRA-MITOCHONDRIAL ACETYL-COA - IMPLICATIONS FOR THE PROBING OF LIPOGENIC ACETYL-COA VIA DRUG ACETYLATIONAND FOR THE PRODUCTION OF ACETATE BY THE LIVER

The labeling of liver extra-mitochondrial acetyl-CoA was investigated in isolated rat livers perfused with [2-C-13]acetate, [1-C-13]]octanoa te, or [1,2,3,4-C-13(4)]docosanoate and with drugs that undergo acetyl ation (phenylaminobutyrate, paraaminobenzoate, and sulfamethoxazole; s ingly or in combination). The C-13 enrichment of mitochondrial acetyl- CoA was probed by the enrichment of R-beta-hydroxybutyrate. The latter was not enriched from [1,2,3,4-C-13(4)]docosanoate, thus excluding mi tochondrial beta-oxidation of docosanoate. The C-13 enrichment of extr a-mitochondrial acetyl-CoA was probed by the enrichments of acetylated drugs and of free acetate. In most cases, the four probes yielded dif ferent enrichments. Thus, extra-mitochondrial acetyl-CoA appears nonho mogeneous. Competition between drugs alters the labeling of individual acetyl-CoA sub. pools. The labeling pattern of acetylated drugs sugge sts the existence of more than the two N-acetyltransferases identified so far by others. Our data question the possibility of probing the po ol of lipogenic acetyl-CoA via drug acetylation.