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Title: Binding of a valproate metabolite to the trifunctional protein of fatty acid oxidation.
Austin Authors: Baldwin, Graham S;Abbott, F S;Nau, H
Affiliation: Department of Surgery, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 8-Apr-1996
Publication information: Febs Letters; 384(1): 58-60
Abstract: The anti-convulsant drug valproate causes hepatic failure in a small percentage of patients. We now report that the valproate metabolite 2,4-dien-valproate binds (IC50 = 42 microM) to the alpha-subunit of the trifunctional protein responsible for the second and third steps in the mitochondrial beta-oxidation of fatty acids. Binding of valproate itself, or of the metabolites 2-envalproate, 4-en-valproate or 3-hydroxy-4-en-valproate, is considerably weaker. We conclude that valproate-induced hepatotoxicity may be due in part to the reversible binding of the valproate metabolite 2,4-dien-valproate or its CoA ester to the alpha-subunit of the trifunctional protein with consequent inhibition of fatty acid oxidation.
Gov't Doc #: 8797803
Journal: FEBS letters
Type: Journal Article
Subjects: Animals
Fatty Acids.metabolism
Gastric Mucosa.metabolism
Liver.drug effects.pathology
Macromolecular Substances
Mitochondrial Trifunctional Protein
Multienzyme Complexes.isolation & purification.metabolism
Protein Binding
Valproic Acid.analogs & derivatives.metabolism.toxicity
Appears in Collections:Journal articles

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