1997 Volume 121 Issue 3 Pages 506-513
The second and third reactions of the peroxisomal β-oxidation spiral are thought to be catalyzed by enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase bifunctional pro-tein(L-bifunctional protein). Recently, we found the presence of D-3-hydroxyacyl-CoA dehyd-atase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-bifunctional protein) in mammalian peroxisomes. Therefore, we studied the physiological role of the 0-bifunctional protein. The contents of the L-and 0-bifunctional proteins were about 0.01 and 0.5 pg/mg protein, respectively, in cultured human skin fibroblasts. The activity of conversion of hexadecenoyl-CoA to 3-ketopalmitoyl-CoA by the D-bifunctional protein was estimated to be about 0.5 milliunit/mg of fibroblast protein. This value was about 100-fold that of the L-bifunctional protein in the fibroblasts. From comparison of the activities of the bifunctional proteins with the rate of palmitate oxidation and the activities of acyl-CoA oxidase and 3-ketoacyl-CoA thiolase, it is proposed that the D-bifunctional protein plays a major role in the peroxisomal oxidation of palmitate in the fibroblasts. The contents of both the L-and D-bifunctional proteins in liver were about 2.5μg/mg protein. Therefore, it is suggested that the 0-bifunctional protein also plays a significant role in human liver peroxisomal fatty acid oxidation. Actions of the bifunctional proteins on enoyl forms of other acyl-CoA derivatives were examined. The D-bifunctional protein but not the L- bifunc-tional protein reacted with 2-methylhexadecenoyl-CoA and 3α, 7α, 12 α-trihydroxy-5β-cholest-24-enoyl -CoA. We propose that, among the reactions of the distinct group of carboxylates oxidized specifically in peroxisomes, oxidation of 2-methyl-branched fatty acids and side-chain shortening of cholesterol for bile acid formation are catalyzed by the D-bifunctional protein, but not the L-bifunctional protein.
