Journal of Inherited Metabolic Disease

, Volume 31, Issue 2, pp 205–216

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

DOI: 10.1007/s10545-008-0841-x

Cite this article as:
Silva, M.F.B., Aires, C.C.P., Luis, P.B.M. et al. J Inherit Metab Dis (2008) 31: 205. doi:10.1007/s10545-008-0841-x

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.

Abbreviations

CoA

coenzyme A

DILI

drug-induced liver injury

FAO

fatty acid β-oxidation

FFA

free fatty acids

IEM

inborn error of metabolism

RLM

rat liver mitochondria

VPA

valproic acid

Copyright information

© 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