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 acyl-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 docosahexaenoic acid, arachidonic acid, 4,7,10-cis-hexadecatrienoic acid, 5-cis-tetradecenoic acid, and 4-cis-decenoic acid were effectively dehydrogenated 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 removed from the thioester function. Although bovine LCAD effectively dehydrogenated 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 efficiency determined with tetradecanoyl-CoA, whereas LCAD acted equally well on both substrates. The conclusion of this study is that LCAD serves an important, if not essential function in the beta-oxidation of unsaturated fatty acids.
Lea
W
W
Department of Chemistry, City College of the City University of New York, NY 10031, USA.
Abbas
A S
AS
Sprecher
H
H
Vockley
J
J
Schulz
H
H
D000214:Acyl Coenzyme A / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D051381:Rats; D013379:Substrate Specificity
D000214:Acyl Coenzyme A; D005231:Fatty Acids, Unsaturated; C017585:oleoyl-coenzyme A; C017725:stearoyl-coenzyme A; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain