Long-chain acyl-CoA dehydrogenase is a key enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids

The first reaction of mitochondrial beta-oxidation, which is catalyzed by a cyl-CoA dehydrogenases, was studied with unsaturated fatty acids that have a double bond either at the 4,5 or 5,6 position. The CoA thioesters of doco sahexaenoic acid, arachidonic acid, 4,7,10-cis-hexadecatrienoic acid, 5-cis -tetradecenoic acid, and 4-cis-decenoic acid were effectively dehydrogenate d by both rat and human long-chain acyl-CoA dehydrogenases (LCAD), whereas they were poor substrates of very long-chain acyl-CoA dehydrogenases (VLCAD ). VLCAD, however, was active with CoA derivatives of long-chain saturated fatty acids or unsaturated fatty acids that have double bonds further remov ed from the thioester function. Although bovine LCAD effectively dehydrogen ated 5-cis-tetradecenoyl-CoA (14:1) and 4,7,10-cis-hexadecatrienoyl-CoA, it was nearly inactive toward the other unsaturated substrates. The catalytic efficiency of rat VLCAD with 14:1 as substrate was only 4% of the efficien cy determined with tetradecanoyl-CoA, whereas LCAD acted equally well on bo th substrates. The conclusion of this study is that LCAD serves an importan t, if not essential function in the beta-oxidation of unsaturated fatty aci ds. (C) 2000 Elsevier Science B.V. All rights reserved.