SSIEM Symposium 2007

Journal of Inherited Metabolic Disease

, Volume 31, Issue 2, pp 205-216

First online:

Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: A review

  • M. F. B. SilvaAffiliated withCentro de Patogénese Molecular-UBMBE, iMed.UL, Faculdade de Farmácia da Universidade de Lisboa Email author 
  • , C. C. P. AiresAffiliated withCentro de Patogénese Molecular-UBMBE, iMed.UL, Faculdade de Farmácia da Universidade de Lisboa
  • , P. B. M. LuisAffiliated withCentro de Patogénese Molecular-UBMBE, iMed.UL, Faculdade de Farmácia da Universidade de Lisboa
  • , J. P. N. RuiterAffiliated withCentro de Patogénese Molecular-UBMBE, iMed.UL, Faculdade de Farmácia da Universidade de Lisboa
  • , L. IJlstAffiliated withCentro de Patogénese Molecular-UBMBE, iMed.UL, Faculdade de Farmácia da Universidade de Lisboa
  • , M. DuranAffiliated withLaboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre, University of Amsterdam
  • , R. J. A. WandersAffiliated withLaboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre, University of Amsterdam
  • , I. Tavares de AlmeidaAffiliated withLaboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical Centre, University of Amsterdam

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Summary

Valproic acid (VPA; 2-n-propylpentanoic acid) is widely used as a major drug in the treatment of epilepsy and in the control of several types of seizures. Being a simple fatty acid, VPA is a substrate for the fatty acid β-oxidation (FAO) pathway, which takes place primarily in mitochondria. The toxicity of valproate has long been considered to be due primarily to its interference with mitochondrial β-oxidation. The metabolism of the drug, its effects on enzymes of FAO and their cofactors such as CoA and/or carnitine will be reviewed. The cumulative consequences of VPA therapy in inborn errors of metabolism (IEMs) and the importance of recognizing an underlying IEM in cases of VPA-induced steatosis and acute liver toxicity are two different concepts that will be emphasized.