ISSN:
1573-739X
Keywords:
Biotransformation
;
Fatty acid oxidation
;
Liver diseases
;
2-n-Propyl-4-pentenoic acid
;
Steatosis
;
Valproic acid
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract A number of lines of evidence indicate that metabolites of valproate rather than the parent drug, mediate the microvesicular steatosis which characterizes valproate-associated liver injury. In this article, two mechanisms are discussed whereby valproate may cause hepatic steatosis through interference with the process of fatty acidβ-oxidation. In the first, valproate itself enters the mitochondrion where it competes for the enzymes and/or co-factors involved in theβ-oxidation of endogeneous substrates, while in the second, valproate is metabolized via the hepatotoxic terminal olefin, Δ4-valproate, to a variety of chemically reactive intermediates which inhibit key enzymes in theβ-oxidation cycle.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01962701
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