Valproate induces in vitro accumulation of long-chain fatty acylcarnitines.

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). Copyright 2001 Academic Press.