Mitochondrial acetyl-CoA acetyltransferase in liver and extrahepatic tissues: role of modification by coenzyme A.
The influence of clofibrate and di(2-ethylhexyl)phthalate on mitochondrial acetyl-CoA acetyltransferase (acetyl-CoA: acetyl-CoA C-acetyltransferase, EC 2.3.1.9), the rate-limiting ketogenic enzyme, which can be modified and inactivated by CoA, was investigated. In fed rats, both compounds induced a doubling of ketone bodies in the blood and, moreover, an increase by about 13% in the hepatic relative amount of the unmodified, i.e., the most active form of the enzyme (immunoreactive protein). This shift would account for an elevation of overall enzyme activity by about 5% only. Thus, the CoA modification of mitochondrial acetyl-CoA acetyltransferase did not explain the entire augmentation of ketone bodies. However, clofibrate and di(2-ethylhexyl)phthalate also increased the immunospecific protein and enzyme activity by approx. 2- and 3-fold, respectively. These effects were observed in liver, but not in several extrahepatic tissues.
Balzer
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Huth
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D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism*; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002994:Clofibrate / Q000494:pharmacology*; D003065:Coenzyme A / Q000378:metabolism*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D007122:Immunoelectrophoresis; D007657:Ketone Bodies / Q000097:blood; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D010795:Phthalic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007657:Ketone Bodies; D010795:Phthalic Acids; D004051:Diethylhexyl Phthalate; D000123:Acetyltransferases; D000101:Acetyl-CoA C-Acetyltransferase; D002994:Clofibrate; D003065:Coenzyme A