Abstract
Unsaturated fatty acids with odd-numbered double bonds, e.g. oleic acid, can be degraded by beta-oxidation via the isomerase-dependent pathway or the reductase-dependent pathway that differ with respect to the metabolism of the double bond. In an attempt to elucidate the metabolic functions of the two pathways and to determine their contributions to the beta-oxidation of unsaturated fatty acids, the degradation of 2-trans,5-cis-tetradecadienoyl-CoA, a metabolite of oleic acid, was studied with rat heart mitochondria. Kinetic measurements of metabolite and cofactor formation demonstrated that more than 80% of oleate beta-oxidation occurs via the classical isomerase-dependent pathway whereas the more recently discovered reductase-dependent pathway is the minor pathway. However, the reductase-dependent pathway is indispensable for the degradation of 3,5-cis-tetradecadienoyl-CoA, which is formed from 2-trans,5-cis-tetradecadienoyl-CoA by delta(3),delta(2)-enoyl-CoA isomerase, the auxiliary enzyme that is essential for the operation of the major pathway of oleate beta-oxidation. The degradation of 3,5-cis-tetradecadienoyl-CoA is limited by the capacity of 2,4-dienoyl-CoA reductase to reduce 2-trans,4-trans-tetradecadienoyl-CoA, which is rapidly formed from its 3,5 isomer by delta(3,5),delta(2,4)-dienoyl-CoA isomerase. It is concluded that both pathways are essential for the degradation of unsaturated fatty acids with odd-numbered double bonds inasmuch as the isomerase-dependent pathway facilitates the major flux through beta-oxidation and the reductase-dependent pathway prevents the accumulation of an otherwise undegradable metabolite.
Highlights
The degradation of unsaturated and polyunsaturated fatty acids by -oxidation requires the involvement of auxiliary enzymes that act on preexisting double bonds
Because it had previously been determined that Triton X-100 at the applied concentration did not affect the activities of the enzymes of the -oxidation spiral [25, 26], it was only necessary to assess how Triton X-100 affects the activities of enoyl-CoA isomerase, 2,4-dienoyl-CoA reductase, and dienoyl-CoA isomerase
Specific activities for the isomerase-dependent pathway are based on initial velocity measurements that were linear during the first 2 min when, on the average, 1.5 mol of NADH were produced per mol of degraded 2-trans,5-cis-tetradecadienoyl-CoA (III)
Summary
The degradation of unsaturated and polyunsaturated fatty acids by -oxidation requires the involvement of auxiliary enzymes that act on preexisting double bonds. In an attempt to elucidate the metabolic functions of the two pathways and to determine their contributions to the -oxidation of unsaturated fatty acids, the degradation of 2-trans,5-cis-tetradecadienoyl-CoA, a metabolite of oleic acid, was studied with rat heart mitochondria.
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