Fatty acid oxidation in mitochondria: The impact of enzyme organization and aspects of unsaturated fatty acids degradation.

摘要

4-Bromotiglic acid, a novel inhibitor of beta-oxidation, was developed as a tool for probing the cooperation between the membrane-bound and soluble beta-oxidation systems of rat liver mitochondria. Long-chain fatty acids seem to be acted upon fast by the membrane-bound beta-oxidation system. The main transfer of intermediates between the two systems probably occurs after the length of the acyl chain has been shortened to 14 or 12 carbon atoms;Differences between the oxidation of cis and trans fatty acids were observed in rat mitochondria. 5-trans -Tetradecenoyl-CoA was found to accumulate in the matrix of both Mt heart and rat liver mitochondria during the oxidation of elaidoyl-CoA at a three-fold higher level than was 5-cis-tetradecenoyl-CoA which is derived from oleoyl-CoA. Other metabolites that accumulated were hexanoyl-CoA and dodecanoyl-CoA regardless of whether saturated or unsaturated long-chain acyl-CoAs served as substrates. The accumulation of these metabolites is possibly due to the organization of beta-oxidation enzymes in the mitochondrial matrix.;The mitochondrial metabolism of conjugated fatty acids was investigated. 5,7-Dienoyl-CoAs are the expected metabolites of polyunsaturated fatty acids with conjugated double bonds at odd-numbered position. After introduction of a 2-trans double bond, the resultant 2,5,7-trienoyl-CoA can either continue its pass through the beta-oxidation cycle or be converted by Delta3,Delta2-enoyl-CoA isomerase to 3,5,7-trienoyl-CoA. The latter compound is isomerized by a novel enzyme, named Delta 3,5,7, Delta2,4,6-trienoyl-CoA isomerase, to 2,4,6-trienoyl-CoA that is a substrate of 2,4-dienoyl-CoA reductase and hence can be completely degraded via beta-oxidation.;2,4-Dienoyl-CoA reductase from E. coli was found to be a novel Fe-S flavoprotein that contains 1 mole of FAD, 1 mole of FMN, 4 moles of Fe and 4 moles of labile sulfur per mole of enzyme. The reductase can be reduced by dithionite or NADPH, and also can undergo photoreduction. It needs approximately 5 electrons for its complete reduction, and requires the removal of 4 to 5 electrons for the oxidation of the reduced enzyme.