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-(13)C]acetate, [1-(13)C]octanoate, or [1,2,3,4-(13)C4]docosanoate and with drugs that undergo acetylation (phenylaminobutyrate, paraaminobenzoate, and sulfamethoxazole; singly or in combination). The 13C enrichment of mitochondrial acetyl-CoA was probed by the enrichment of R-beta-hydroxybutyrate. The latter was not enriched from [1,2,3,4-(13)C4]docosanoate, thus excluding mitochondrial beta-oxidation of docosanoate. The 13C 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.
Zhang
Y
Y
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106.
Agarwal
K C
KC
Beylot
M
M
Soloviev
M V
MV
David
F
F
Reider
M W
MW
Anderson
V E
VE
Tserng
K Y
KY
Brunengraber
H
H
D010129:4-Aminobenzoic Acid / Q000378:metabolism; D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000613:Aminobutyrates / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002210:Caprylates / Q000378:metabolism*; D002247:Carbon Isotopes; D005227:Fatty Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013420:Sulfamethoxazole / Q000378:metabolism
D000085:Acetates; D000613:Aminobutyrates; D002210:Caprylates; D002247:Carbon Isotopes; D005227:Fatty Acids; D000105:Acetyl Coenzyme A; C014328:2-amino-4-phenylbutyric acid; C007547:behenic acid; D013420:Sulfamethoxazole; C031492:octanoic acid; D010129:4-Aminobenzoic Acid