Journal of Inherited Metabolic Disease

, Volume 31, Issue 2, pp 205–216 | Cite as

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

  • M. F. B. Silva
  • C. C. P. Aires
  • P. B. M. Luis
  • J. P. N. Ruiter
  • L. IJlst
  • M. Duran
  • R. J. A. Wanders
  • I. Tavares de Almeida
SSIEM Symposium 2007


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.


Valproic Acid Carnitine Carnitine Supplementation Microvesicular Steatosis Reye Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



coenzyme A


drug-induced liver injury


fatty acid β-oxidation


free fatty acids


inborn error of metabolism


rat liver mitochondria


valproic acid


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© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • M. F. B. Silva
    • 1
  • C. C. P. Aires
    • 1
  • P. B. M. Luis
    • 1
  • J. P. N. Ruiter
    • 1
  • L. IJlst
    • 1
  • M. Duran
    • 2
  • R. J. A. Wanders
    • 2
  • I. Tavares de Almeida
    • 2
  1. 1.Centro de Patogénese Molecular-UBMBE, iMed.ULFaculdade de Farmácia da Universidade de LisboaLisboaPortugal
  2. 2.Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Academic Medical CentreUniversity of AmsterdamAmsterdamThe Netherlands

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