The mechanism of alpha-ketoisocaproate oxygenase. Formation of beta-hydroxyisovalerate from alpha-ketoisocaproate

J Biol Chem. 1982 Jul 10;257(13):7468-71.


A soluble alpha-ketoisocaproate oxygenase from rat liver catalyzes the decarboxylation and hydroxylation of alpha-ketoisocaproate to form beta-hydroxyisovalerate. The source of oxygen (O2 or H2O) enzymatically incorporated into beta-hydroxyisovalerate was investigated using 18O2 and H218O. Greater than 92% of the carboxyl groups of beta-hydroxyisovaleric acid contained 1 18O atom from 18O2 and 15% of the beta-hydroxyl oxygens of beta-hydroxyisovaleric acid contained 18O from 18O2. Since some oxygen of the beta-hydroxyl group is derived from O2 and since others have shown a rapid H2O in equilibrium ROH exchange for similar reactions, we conclude that both of the oxygens of beta-hydroxyisovaleric acid are derived from O2 and that exchange of water oxygen with the beta-hydroxyl group of beta-hydroxyisovaleric acid must occur with an intermediate of the reaction. Thus, the alpha-ketoisocaproate oxygenase would be a dioxygenase. A mechanism consistent with the 18O experiments and other properties of the enzyme is proposed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caproates / metabolism*
  • Dioxygenases*
  • Keto Acids / metabolism*
  • Kinetics
  • Liver / enzymology*
  • Mass Spectrometry
  • Oxygen Isotopes
  • Oxygenases / metabolism*
  • Rats
  • Valerates / metabolism*


  • Caproates
  • Keto Acids
  • Oxygen Isotopes
  • Valerates
  • beta-hydroxyisovaleric acid
  • alpha-ketoisocaproic acid
  • Oxygenases
  • Dioxygenases
  • alpha-ketoisocaproate oxygenase