3-Hydroxyacyl-CoA epimerases of rat liver peroxisomes and Escherichia coli function as auxiliary enzymes in the beta-oxidation of polyunsaturated fatty acids.
The beta-oxidation of 2-trans,4-cis-decadienoyl-CoA, an assumed metabolite of linoleic acid, by purified enzymes from mitochondria, peroxisomes, and Escherichia coli was studied. 2-trans,4-cis-Decadienoyl-CoA is an extremely poor substrate of the beta-oxidation system reconstituted from mitochondrial enzymes. The results of a kinetic evaluation lead to the conclusion that in mitochondria 2-trans,4-cis-decadienoyl-CoA is not directly beta-oxidized, but instead is reduced by NADPH-dependent 2,4-dienoyl-CoA reductase prior to its beta-oxidation. Hence, the mitochondrial beta-oxidation of 2-trans,4-cis-decadienoyl-CoA does not require 3-hydroxyacyl-CoA epimerase, a conclusion which agrees with the finding that 3-hydroxyacyl-CoA epimerase is absent from mitochondria (Chu, C.-H., and Schulz, H. (1985) FEBS Lett. 185, 129-134). However, 2-trans,4-cis-decadienoyl-CoA can be slowly oxidized by the bifunctional beta-oxidation enzyme from rat liver peroxisomes, as well as by the fatty acid oxidation complex from E. coli. The observed rates of 2-trans,4-cis-decadienoyl-CoA degradation by these two multi-functional proteins were significantly higher than the values calculated according to steady-state velocity equations derived for coupled enzyme reactions. This is attributed to the direct transfer of L-3-hydroxy-4-cis-decenoyl-CoA from the active site of enoyl-CoA hydratase to that of 3-hydroxyacyl-CoA dehydrogenase on the same protein molecule. All observations together lead to the suggestion that the chain shortening of 2-trans,4-cis-decadienoyl-CoA in peroxisomes and in E. coli occurs simultaneously by two different pathways. The major pathway involves the NADPH-dependent 2,4-dienoyl-CoA reductase, whereas 3-hydroxyacyl-CoA epimerase functions in the metabolism of D-3-hydroxyoctanoyl-CoA which is formed via the minor pathway.
D000818:Animals; D002417:Cattle; D004926:Escherichia coli / Q000201:enzymology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000648:ultrastructure*; D008830:Microbodies / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology; D008956:Models, Chemical; D010084:Oxidation-Reduction; D019998:Racemases and Epimerases / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D007535:Isomerases; D019998:Racemases and Epimerases; C029601:3-hydroxybutyryl-CoA epimerase