NADPH-dependent beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms.
The mitochondrial metabolism of 5-enoyl-CoAs, which are formed during the beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms, was studied with mitochondrial extracts and purified enzymes of beta-oxidation. Metabolites were identified spectrophotometrically and by high performance liquid chromatography. 5-cis-Octenoyl-CoA, a putative metabolite of linolenic acid, was efficiently dehydrogenated by medium-chain acyl-CoA dehydrogenase (EC 1.3.99.3) to 2-trans-5-cis-octadienoyl-CoA, which was isomerized to 3,5-octadienoyl-CoA either by mitochondrial delta 3,delta 2-enoyl-CoA isomerase (EC 5.3.3.8) or by peroxisomal trifunctional enzyme. Further isomerization of 3,5-octadienoyl-CoA to 2-trans-4-trans-octadienoyl-CoA in the presence of soluble extracts of either rat liver or rat heart mitochondria was observed and attributed to a delta 3,5,delta 2,4-dienoyl-CoA isomerase. Qualitatively similar results were obtained with 2-trans-5-trans-octadienoyl-CoA formed by dehydrogenation of 5-trans-octenoyl-CoA. 2-trans-4-trans-Octadienoyl-CoA was a substrate for NADPH-dependent 2,4-dienoyl-CoA reductase (EC 1.3.1.34). A soluble extract of rat liver mitochondria catalyzed the isomerization of 2-trans-5-cis-octadienoyl-CoA to 2-trans-4-trans-octadienoyl-CoA, which upon addition of NADPH, NAD+, and CoA was chain-shortened to hexanoyl-CoA, butyryl-CoA, and acetyl-CoA. Thus we conclude that odd-numbered double bonds, like even-numbered double bonds, can be reductively removed during the beta-oxidation of polyunsaturated fatty acids.
Smeland
T E
TE
Department of Chemistry, City College, City University of New York, New York 10031.
Nada
M
M
Cuebas
D
D
Schulz
H
H
D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism*; D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism*; D000818:Animals; D002175:Candida / Q000201:enzymology; D019748:Carbon-Carbon Double Bond Isomerases; D002417:Cattle; D064006:Dodecenoyl-CoA Isomerase; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008830:Microbodies / Q000201:enzymology; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D000214:Acyl Coenzyme A; D005231:Fatty Acids, Unsaturated; D009249:NADP; D044944:Acyl-CoA Dehydrogenases; D000102:Acetyl-CoA C-Acyltransferase; C070004:2,4-dienoyl-CoA hydratase; D004746:Enoyl-CoA Hydratase; D007535:Isomerases; D019748:Carbon-Carbon Double Bond Isomerases; D064006:Dodecenoyl-CoA Isomerase