Significance of the reductase-dependent pathway for the beta-oxidation of unsaturated fatty acids with odd-numbered double bonds. Mitochondrial metabolism of 2-trans-5-cis-octadienoyl-CoA.
The beta-oxidation of unsaturated fatty acids with odd-numbered double bonds proceeds by reduction of the double bond (reductase-dependent pathway) in addition to the well established isomerization of the double bond (isomerase-dependent pathway). The metabolic significance of the reductase-dependent pathway was assessed with 2-trans-5-cis-octadienoyl-CoA (2,5-octadienoyl-CoA) and its products, all of which are metabolites of alpha-linolenic acid. A kinetic evaluation of beta-oxidation enzymes revealed that the presence of a 5-cis double bond in the substrate most adversely affected the activity of 3-ketoacyl-CoA thiolase although not enough to become rate-limiting. Concentration-dependent and time-dependent measurements indicated that most (80%) of 2,5-octadienoyl-CoA is metabolized via the isomerase-dependent pathway. The reason for the greater flux through the isomerase-dependent pathway is the higher activity of L-3-hydroxyacyl-CoA dehydrogenase as compared with Delta3,Delta2-enoyl-CoA isomerase. These two enzymes catalyze the rate-limiting steps in the isomerase-dependent and reductase-dependent pathways, respectively. Once 2,5-octadienoyl-CoA is converted to 3,5-octadienoyl-CoA (perhaps fortuitously because of the presence of Delta3,Delta2-enoyl-CoA isomerase), the only effective route for its degradation is via the reductase-dependent pathway. It is concluded that the reductase-dependent pathway assures the degradation of 3,5-dienoyl-CoA intermediates, thereby preventing the depletion of free coenzyme A and a likely impairment of mitochondrial oxidative function.
Shoukry
K
K
Department of Chemistry, City College, City University of New York, New York, New York 10031, USA.
Schulz
H
H
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats
C111365:2,5-octadienoyl-coenzyme A; D000214:Acyl Coenzyme A; D005231:Fatty Acids, Unsaturated; D010088:Oxidoreductases