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).
Silva
M F
MF
Department of Clinical Chemistry and Paediatrics, University of Amsterdam, Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
Jakobs
C
C
Duran
M
M
de Almeida
I T
IT
Wanders
R J
RJ
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*
D005227:Fatty Acids; D009097:Multienzyme Complexes; C116917:acylcarnitine; D019308:Palmitic Acid; D014635:Valproic Acid; D063991:Mitochondrial Trifunctional Protein; D002331:Carnitine