Acetate generation in rat liver mitochondria; acetyl-CoA hydrolase activity is demonstrated by 3-ketoacyl-CoA thiolase

Biochim Biophys Acta. 2006 Jan;1761(1):17-23. doi: 10.1016/j.bbalip.2006.01.001. Epub 2006 Jan 30.


Acetate has been found as an endogenous metabolite of beta-oxidation of fatty acids in liver. In order to investigate the regulation of acetate generation in liver mitochondria, we attempted to purify a mitochondrial acetyl-CoA hydrolase in rat liver. This acetyl-CoA-hydrolyzing activity in isolated mitochondria was induced by the treatment of rats with di(2-ehtylhexyl)phthalate (DEHP), a peroxisome proliferator which induces expression of several peroxisomal and mitochondrial enzymes involved in beta-oxidation of fatty acids. The purified enzyme was 43-kDa in molecular mass by SDS/PAGE. Internal amino acid sequencing of this enzyme revealed that it was identical with mitochondrial 3-ketoacyl-CoA thiolase, suggesting that this enzyme has two kinds of activities, 3-ketoacyl-CoA thiolase and acetyl-CoA hydrolase activities. Kinetic studies clearly indicated that this enzyme had the both activities and each activity was inhibited by the substrates of the other activity, that is, 3-ketoacyl-CoA thiolase activity was inhibited by acetyl-CoA, on the other hand, acetyl-CoA hydrolase activity was inhibited by acetoacetyl-CoA in a competitive manner. These findings suggested that acetate generation in liver mitochondria is a side reaction of this known enzyme, 3-ketoacyl-CoA thiolase, and this enzyme may regulate its activities depending on each substrate level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism*
  • Acetyl-CoA C-Acyltransferase / metabolism*
  • Acetyl-CoA Hydrolase / isolation & purification
  • Acetyl-CoA Hydrolase / metabolism*
  • Acyl Coenzyme A / metabolism
  • Animals
  • Chromatography, Gel
  • Diethylhexyl Phthalate / pharmacology
  • Enzyme Activation
  • Kinetics
  • Male
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / enzymology
  • Mitochondria, Liver / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Acetates
  • Acyl Coenzyme A
  • Diethylhexyl Phthalate
  • Acetyl-CoA C-Acyltransferase
  • Acetyl-CoA Hydrolase