Δ3,5,7,Δ2,4,6-Trienoyl-CoA Isomerase, a Novel Enzyme That Functions in the β-Oxidation of Polyunsaturated Fatty Acids with Conjugated Double Bonds

Abstract

The mitochondrial metabolism of unsaturated fatty acids with conjugated double bonds at odd-numbered positions, e.g. 9-cis,11-trans-octadecadienoic acid, was investigated. These fatty acids are substrates of ␤-oxidation in isolated rat liver mitochondria and hence are expected to yield 5,7-dienoyl-CoA intermediates. 5,7-Decadienoyl-CoA was used to study the degradation of these intermediates. After introduction of a 2-trans-double bond by acyl-CoA dehydrogenase or acyl-CoA oxidase, the resultant 2,5,7-decatrienoyl-CoA can either continue its pass through the ␤-oxidation cycle or be converted by ⌬ 3 ,⌬ 2 -enoyl-CoA isomerase to 3,5,7-decatrienoyl-CoA. The latter compound was isomerized by a novel enzyme, named ⌬ 3,5,7 ,⌬ 2,4,6 -trienoyl-CoA isomerase, to 2,4,6-decatrienoyl-CoA, which is a substrate of 2,4-dienoyl-CoA reductase (Wang, H.-Y. and Schulz, H. (1989) Biochem. J. 264, 47-52) and hence can be completely degraded via ␤-oxidation. ⌬ 3,5,7 ,⌬ 2,4,6 -TrienoylCoA isomerase was purified from pig heart to apparent homogeneity and found to be a component enzyme of ⌬ 3,5 ,⌬ 2,4 -dienoyl-CoA isomerase. Although the direct ␤-oxidation of 2,5,7-decatrienoyl-CoA seems to be the major pathway, the degradation via 2,4,6-trienoyl-CoA makes a significant contribution to the total ␤-oxidation of this intermediate.The ␤-oxidation of typical polyunsaturated fatty acids requires the involvement of three auxiliary enzymes in addition to the enzymes that catalyze the four basic reactions of the ␤-oxidation spiral (1). The auxiliary enzymes are ⌬ 3 ,⌬ 2 -enoylCoA isomerase (⌬ 3 -cis-⌬ 2 -trans-enoyl-CoA isomerase, EC 5.3.3.8; referred to hereafter as enoyl-CoA isomerase), 2,4-dienoyl-CoA reductase (4-enoyl-CoA reductase (NADPH), EC 1.3.1.34), and ⌬ 3,5 ,⌬ 2,4 -dienoyl-CoA isomerase (referred to hereafter as dienoyl-CoA isomerase). These enzymes catalyze either the reduction or isomerization of double bonds once the double bonds are close to the thioester function as the result of chain shortening. Consequently, double bonds either are reductively removed or are shifted to yield 2-trans-enoyl-CoAs, which are intermediates of the ␤-oxidation spiral. Polyunsaturated fatty acid with conjugated double bonds may yield intermediates with more extended chromophores. For example, a fatty acid with two conjugated double bonds at even-numbered positions is assumed to be chain-shortened by ␤-oxidation to 4,6-dienoyl-CoA and is then converted to 2,4,6-trienoyl-CoA by acyl-CoA dehydrogenase. The further metabolism of this intermediate is facilitated by 2,4-dienoyl-CoA reductase, which catalyzes the reduction of one double bond of the 2,4,6-trienoylCoA chromophore to yield 3,6-dienoyl-CoA (2).The ␤-oxidation of a fatty acid with two conjugated double bonds at odd-numbered positions would produce 5,7-dienoylCoA, which may be dehydrogenated by acyl-CoA dehydrogenase to 2,5,7-trienoyl-CoA. The latter compound may be chainshortened to 3,5-dienoyl-CoA or isomerized to 3,5,7-trienoylCoA by enoyl-CoA isomerase. The further metabolism of 3,5,7-trieno...

Lipoxygenase-mediated metabolism of storage lipids in germinating sunflower cotyledons and ?-oxidation of (9Z,11E,13S)-13-hydroxy-octadeca-9,11-dienoic acid by the cotyledonary glyoxysomes

“…When this fatty acid was used as b-oxidation substrate in the absence of NADPH, substantial amounts of short-chain intermediates were detected. This observation indicates that glyoxysomes possess the capacity to metabolize Z,E-conjugated dienes via a pathway that involves a dienoyl-CoA isomerase but not a dienoyl-CoA reductase, as has been shown for rat liver and yeast (Liang et al 1999;Shoukry and Schulz 1998). Consequently, the occurrence of the Z,E-conjugated diene may not be the mechanistic reason for the metabolic arrest during b-oxidation of 13-H(K)ODE.…”

“…However, complete breakdown of 13-HODE to acetyl-CoA can be achieved theoretically in analogy to the breakdown of conjugated linoleic acid [(9Z,11E)-octadeca-9,11-dienoic acid; Shoukry and Schulz 1998;Liang et al 1999;Gurvitz et al 2001]. In addition to the enzymes of the classic b-oxidation cascade this pathway requires di-/trienoyl-CoA isomerase with or without dienoyl-CoA reductase.…”

Disturbance in uniformly13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele

“…This difference in retention v. oxidation of DHA in E4+ is consistent with our previous report that the increase in plasma DHA after supplementing with EPA+DHA was lower in E4+ than in E4 − ( 19 ) . β-Oxidation of DHA is thought to be mainly conducted in peroxisomes ( 46 ) , but the relative contribution of peroxisomal v. mitochondrial β-oxidation to the whole-body production of 13 CO 2 from [ 13 C]DHA in humans is unknown. To the best of our knowledge, there are currently no available data supporting a potential role of APOE4 polymorphism on the expression and/or activity of these peroxisomal enzymes β-oxidising DHA.…”

High-Resolution Metabolomics with Acyl-CoA Profiling Reveals Widespread Remodeling in Response to Diet*

“…5 and 6), and an increase of propionyl-carnitine in serum of HF fed mouse has been reported (21). C10:3-CoA is an intermediate involved in unsaturated fatty acid metabolism, such as linoleic acid or conjugated linoleic acid (31), which indicates that unsaturated fatty acid metabolism is also altered even though they only occupy a very small portion of the HF diet. The increase of C16 and C18 acyl-CoA reflects the increase of fatty acid oxidation induced by high fat diet.…”