NONHOMOGENEOUS LABELING OF LIVER EXTRA-MITOCHONDRIAL ACETYL-COA - IMPLICATIONS FOR THE PROBING OF LIPOGENIC ACETYL-COA VIA DRUG ACETYLATION AND 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]]octanoate, or [1,2,3,4-C-13(4)]docosanoate and with drugs that undergo acetylation (phenylaminobutyrate, paraaminobenzoate, and sulfamethoxazole; singly 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 mitochondrial beta-oxidation of docosanoate. The C-13 enrichment of extra-mitochondrial acetyl-CoA was probed by the enrichments of acetylated drugs and of free acetate. In most cases, the four probes yielded different enrichments. Thus, extra-mitochondrial acetyl-CoA appears nonhomogeneous. Competition between drugs alters the labeling of individual acetyl-CoA sub. pools. The labeling pattern of acetylated drugs suggests the existence of more than the two N-acetyltransferases identified so far by others. Our data question the possibility of probing the pool of lipogenic acetyl-CoA via drug acetylation.