Mammalian fatty acid synthetase. III. Characterization of human liver synthetase products and kinetics of methylmalonyl-CoA inhibition

Can J Biochem. 1976 Nov;54(11):923-6. doi: 10.1139/o76-133.


When propionyl-CoA was substituted for either acetyl-CoA or butyryl-CoA in the presence of [14C]malonyl-CoA and NADPH, the pure human liver fatty acids synthetase complex synthesized only straight-chain, saturated, 15- and 17-carbon radioactive fatty acids. At optimal concentrations, propionyl-CoA was a better primer of fatty acid synthesis than acetyl-CoA. Methylmalonyl-CoA inhibited the synthetase competitively with respect to malonyl-CoA. The Ki was calculated to be 8.4 muM. These findings provide an in vitro model and offer a direct explanation at the molecular level for some of the abnormal manifestations observed in diseases characterized by increased cellular concentrations of propionyl-CoA and methylmalonyl-CoA.

MeSH terms

  • Chromatography, Gas
  • Coenzyme A / pharmacology*
  • Fatty Acid Synthases / metabolism*
  • Humans
  • Kinetics
  • Liver / enzymology*
  • Malonates / pharmacology*
  • Methylmalonic Acid / pharmacology*


  • Malonates
  • Methylmalonic Acid
  • Fatty Acid Synthases
  • Coenzyme A