Vamecq, J.
Vallee, L.
Fontaine, M.
Lambert, Didier
[UCL]
Poupaert, Jacques
[UCL]
Nuyts, JP.
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 DELTA4-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.
- Vamecq, Essays Biochem., 24, 115 (1989)
- Lazarow P. B., De Duve C., A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug., 10.1073/pnas.73.6.2043
- Ikeda, J. Biol. Chem., 258, 1066 (1983)
- Besrat, J. Biol. Chem., 244, 1461 (1969)
- Chalmers R. A., Lawson A. M., Organic Acids in Man, ISBN:9789400957800, 10.1007/978-94-009-5778-7
- Casteels, J. Biol. Chem., 263, 2654 (1988)
- Pedersen, Biochem. Int., 17, 163 (1988)
- Casteels, J. Lipid Res., 31, 1865 (1990)
- Farrants Ann-Kristin Östlund, Björkhem Ingemar, Pedersen Jan I., Differential induction of peroxisomal oxidation of palmitic acid and 3α,7α,12α-trihydroxy-5β-cholestanoic acid in rat liver, 10.1016/0005-2760(90)90185-z
- Schepers, J. Biol. Chem., 265, 5242 (1990)
- Vanhove, J. Biol. Chem., 266, 24670 (1991)
- Van, J. Biol. Chem., 256, 24676 (1991)
- ITO M, IKEDA Y, ARNEZ J, FINOCCHIARO G, TANAKA K, The enzymatic basis for the metabolism and inhibitory effects of valproic acid: dehydrogenation of valproyl-CoA by 2-methyl-branched-chain acyl-CoA dehydrogenase, 10.1016/0304-4165(90)90079-c
- Li. Jianxun, Norwood Daniel L., Mao Li Feng, Schulz Horst, Mitochondrial metabolism of valproic acid, 10.1021/bi00216a012
- EYSSEN H, PARMENTIER G, COMPERNOLLE F, BOON J, EGGERMONT E, Trihydroxycoprostanic acid in the duodenal fluid of two children with intrahepatic bile duct anomalies, 10.1016/0304-4165(72)90209-7
- Webster Leslie T., Killenberg Paul G., [57] Coenzyme a thioesters of benzoic, hydroxybenzoic, phenylacetic, and bile acids, Methods in Enzymology (1981) ISBN:9780121819774 p.430-436, 10.1016/s0076-6879(81)77059-9
- Vamecq, Am. J. Physiol., 256, G680 (1989)
- Vamecq Joseph, Fluorometric assay of peroxisomal oxidases, 10.1016/0003-2697(90)90092-n
- Lazarow, J. Biol. Chem., 253, 1522 (1978)
- VAMECQ Joseph, HOFFMANN Edmond, HOOF Francois, Mitochondrial and peroxisomal metabolism of glutaryl-CoA, 10.1111/j.1432-1033.1985.tb08702.x
- Vamecq J, Van Hoof F, Implication of a peroxisomal enzyme in the catabolism of glutaryl-CoA, 10.1042/bj2210203
- Veitch R K, Sherratt H S A, Bartlett K, Organic aciduria in rats made resistant to hypoglycin toxicity by pretreatment with clofibrate, 10.1042/bj2460775
- Veitch K, Draye J P, Van Hoof F, Sherratt H S A, Effects of riboflavin deficiency and clofibrate treatment on the five acyl-CoA dehydrogenases in rat liver mitochondria, 10.1042/bj2540477
- May, J. Biol. Chem., 255, 8394 (1980)
- VAMECQ Joseph, DRAYE Jean-Pierre, Interactions between the ω- and β-Oxidations of Fatty Acids1, 10.1093/oxfordjournals.jbchem.a122035
- Vamecq J, Schepers L, Parmentier G, Mannaerts G P, Inhibition of peroxisomal fatty acyl-CoA oxidase by antimycin A, 10.1042/bj2480603
- Van den Branden Christiane, Roels Frank, Peroxisomal β-oxidation and sodium valproate, 10.1016/0006-2952(85)90409-5
- Granneman G. Richard, Wang Shyh-Ing, Kesterson James W., Machinist Joseph M., The Hepatotoxicity of Valproic Acid and Its Metabolites in Rats. II. Intermediary and Valproic Acid Metabolism, 10.1002/hep.1840040610
- Kesterson James W., Granneman G. Richard, Machinist Joseph M., The Hepatotoxicity of Valproic Acid and Its Metabolites in Rats. I. Toxicologic, Biochemical and Histopathologic Studies, 10.1002/hep.1840040609
- Vamecq J, de Hoffmann E, Van Hoof F, The microsomal dicarboxylyl-CoA synthetase, 10.1042/bj2300683
Référence bibliographique |
Vamecq, J. ; Vallee, L. ; Fontaine, M. ; Lambert, Didier ; Poupaert, Jacques ; et. al. Coa Esters of Valproic Acid and Related Metabolites Are Oxidized in Peroxisomes Through a Pathway Distinct From Peroxisomal Fatty and Bile Acyl-coa Beta-oxidation. In: FEBS Letters, Vol. 322, no. 2, p. 95-100 (1993) |
Permalien |
http://hdl.handle.net/2078.1/49751 |