CoA esters of valproic acid and related metabolites are oxidized in peroxisomes through a pathway distinct from peroxisomal fatty and bile acyl-CoA β-oxidation
| Autor: | Louis Vallée, Joseph Vamecq, Jacques Poupaert, Monique Fontaine, Jean-Pierre Nuyts, Didier M. Lambert |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Fatty Acid Desaturases
Male Valproyl-CoA oxidase Fatty acyl-CoA oxidase Biophysics In Vitro Techniques Biochemistry Microbodies Trihydroxycoprostanoate Bile Acids and Salts Acyl-CoA chemistry.chemical_compound Structural Biology Genetics medicine Acyl-CoA oxidase Animals Clofibrate Enzyme inducer Rats Wistar Molecular Biology Bile acyl-CoA oxidase chemistry.chemical_classification Oxidase test biology Peroxisomal β-oxidation Valproic Acid Fatty Acids Fatty acid Valproate metabolism Cell Biology Hydrogen Peroxide Peroxisome Rats Enzyme chemistry Liver Enzyme Induction biology.protein Acyl Coenzyme A medicine.drug |
| Zdroj: | FEBS Letters. (2):95-100 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/0014-5793(93)81545-B |
| Popis: | In rat liver homogenates fortified with the appropriate cofactors (ATP and CoA), valproic acid induced H2O2 production rates by far lower than those recorded on the straight medium-chain fatty acid n-octanoic acid. Using directly the CoA esters of these carboxylic acids as substrates for the rat liver H2O2-generating enzyme activities, valproyl-CoA, and n-octanoyl-CoA were found to induce similar oxidation rates. In the rat liver homogenates, cyanide-insensitive valproyl-CoA and octanoyl-CoA oxidations occurred at rates similar to those of valproyl-CoA and octanoyl-CoA oxidase(s), respectively. Studies on fractions obtained from rat liver postnuclear supernatants by isopycnic centrifugation on a linear sucrose density gradient disclose that the density distribution of valproyl-CoA oxidase superimposes to those of catalase, fatty acyl-CoA oxidase and cyanide-insensitive fatty acyl-CoA oxidation, three peroxisomal marker activities. By contrast, the cyanide-insensitive valproyl-CoA oxidation does not adopt the typical peroxisomal distribution of these activities but rather exhibits a mitochondrial localization with, however, a minor peroxisomal component. Interestingly enough, the comparative study of rat tissue distribution, inducibility by clofibrate and sensitivity to deoxycholate indicated that valproyl-CoA oxidase is an enzyme distinct from fatty acyl-CoA oxidase and bile acyl-CoA oxidase. Taken as a whole, the results presented here support the occurrence of a peroxisomal oxidation of the CoA ester of valproic acid and its delta 4-enoic derivate which might be characterized by two major features: initiation by an acyl-CoA oxidase distinct from fatty and bile acyl-CoA oxidases, and inability to complete the beta-oxidation cycle which would not proceed, at significant rates, further than the beta-hydroxyacyl-CoA dehydrogenation step in peroxisomes. |
| Databáze: | OpenAIRE |
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