Valproate Induces in Vitro Accumulation of Long-Chain Fatty Acylcarnitines

Abstract

To elucidate the interference mechanisms of valproate (VPA) with mitochondrial fatty acid β-oxidation (FAO), the profile of acylcarnitine formation was studied in vitro. Human fibroblasts were incubated with 0.2 mmol/L [U-13C]palmitate, 0.4 mmol/L l-carnitine, ± VPA (2 mmol/L) (96 h at 37°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).