title: Valproate induces in vitro accumulation of long-chain fatty acylcarnitines.
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).
authors.affiliation: Department of Clinical Chemistry and Paediatrics, University of Amsterdam, Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
authors.forename: M F
authors.initials: MF
authors.lastname: Silva
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: I T
authors.initials: IT
authors.lastname: de Almeida
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D002331:Carnitine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000172:deficiency / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D009097:Multienzyme Complexes; C116917:acylcarnitine; D019308:Palmitic Acid; D014635:Valproic Acid; D063991:Mitochondrial Trifunctional Protein; D002331:Carnitine