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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 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/13462 | Journal: | FEBS letters | URL: | https://pubmed.ncbi.nlm.nih.gov/8797803 | Type: | Journal Article | Subjects: | Animals Anticonvulsants.metabolism.toxicity Fatty Acids.metabolism Gastric Mucosa.metabolism Kinetics Liver.drug effects.pathology Macromolecular Substances Mitochondrial Trifunctional Protein Multienzyme Complexes.isolation & purification.metabolism Oxidation-Reduction Protein Binding Swine Valproic Acid.analogs & derivatives.metabolism.toxicity |
Appears in Collections: | Journal articles |
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