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Formation of a free acyl adenylate during the activation of 2-propylpentanoic acid. Valproyl-AMP: a novel cellular metabolite of valproic acid.

Publication ,  Journal Article
Mao, LF; Millington, DS; Schulz, H
Published in: J Biol Chem
February 15, 1992

A study of the activation of valproic acid (2-n-propylpentanoic acid) by a soluble extract of rat liver mitochondria in the presence of ATP, CoASH, and MgCl2 revealed that, in addition to valproyl-CoA, an unknown UV-absorbing compound is formed which is the sole product when CoASH is omitted from the incubation mixture. The unknown compound, which was purified by high performance liquid chromatography, was identified as valproyl adenylate (valproyl-AMP) by mass spectrometry and by its enzymatic conversion to valproyl-CoA in the presence of CoASH. Valproyl-AMP exists, at least partially, in a free, not-enzyme-bound form. Its rate of formation is linear with time and increases 5-fold when the pH is decreased from 8 to 6.8. Valproyl-AMP was also identified when the metabolism of valproate was investigated with rat liver mitochondria and rat hepatocytes. Since the synthesis of valproyl-AMP is inhibited by octanoate, medium-chain acyl-CoA synthetase (EC. 6.2.1.2) may be responsible for its formation. This study establishes that during the activation of valproic acid to valproyl-CoA free valproyl-AMP is formed which is a novel cellular metabolite of valproic acid.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

February 15, 1992

Volume

267

Issue

5

Start / End Page

3143 / 3146

Location

United States

Related Subject Headings

  • Valproic Acid
  • Rats
  • Mitochondria, Liver
  • Mitochondria, Heart
  • Liver
  • Kinetics
  • Chromatography, High Pressure Liquid
  • Cells, Cultured
  • Caprylates
  • Biochemistry & Molecular Biology
 

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

February 15, 1992

Volume

267

Issue

5

Start / End Page

3143 / 3146

Location

United States

Related Subject Headings

  • Valproic Acid
  • Rats
  • Mitochondria, Liver
  • Mitochondria, Heart
  • Liver
  • Kinetics
  • Chromatography, High Pressure Liquid
  • Cells, Cultured
  • Caprylates
  • Biochemistry & Molecular Biology