Valproate induces in vitro accumulation of long-chain fatty acylcarnitines

Mol Genet Metab. 2001 Aug;73(4):358-61. doi: 10.1006/mgme.2001.3200.

Abstract

To elucidate the interference mechanisms of valproate (VPA) with mitochondrial fatty acid beta-oxidation (FAO), the profile of acylcarnitine formation was studied in vitro. Human fibroblasts were incubated with 0.2 mmol/L [U-(13)C]palmitate, 0.4 mmol/L l-carnitine, +/- VPA (2 mmol/L) (96 h at 37 degrees C). Acylcarnitines (AC) were analyzed by GC-CI-MS. VPA induced an impaired production of acetylcarnitine (C2) and an increase on long-chain AC (C10 to C16) both in control and in FAO-deficient cell lines (VLCAD, LCHAD, MTP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carnitine / analogs & derivatives*
  • Carnitine / chemistry*
  • Carnitine / metabolism*
  • Cell Line
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism*
  • Fibroblasts
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Mitochondrial Trifunctional Protein
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / metabolism
  • Palmitic Acid / metabolism
  • Valproic Acid / pharmacology*

Substances

  • Fatty Acids
  • Multienzyme Complexes
  • acylcarnitine
  • Palmitic Acid
  • Valproic Acid
  • Mitochondrial Trifunctional Protein
  • Carnitine