Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review.
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 beta-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 beta-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.
Silva
M F B
MF
Centro de Patogénese Molecular-UBMBE, iMed.UL, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal. mbsilva@ff.ul.pt
Aires
C C P
CC
Luis
P B M
PB
Ruiter
J P N
JP
IJlst
L
L
Duran
M
M
Wanders
R J A
RJ
Tavares de Almeida
I
I
D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018570:Risk Assessment; D012307:Risk Factors; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000633:toxicity*
D000927:Anticonvulsants; D005227:Fatty Acids; D014635:Valproic Acid