Oxidation of cis-5-unsaturated fatty acids in intact rat liver mitochondria: the operation of reduction pathways.

The metabolism of cis-5 unsaturated fatty acids was studied in intact rat liver mitochondria to assess the operation of a reduction pathway. By using direct quantification of metabolites with a capillary-column gas chromatography, 3-hydroxydodecanoate was identified among other metabolites when cis-5-dodecenoate was metabolized in intact rat liver mitochondria. The formation of 3-hydroxydodecanoate supports the existence of a reduction pathway in the metabolism of cis-5-unsaturated fatty acids. This metabolite cannot be produced from the conventional isomerase-mediated pathway. However, the data also indicated the possible operation of the conventional isomerase-mediated pathway in intact rat liver mitochondria. The reduction pathway appears to account for at least 61% of the pathway for cis-5-dodecenoate. This reduction pathway was likely to proceed from the dehydrogenation to trans-2,cis-5-dodecadienoyl-CoA, which was isomerized to delta 3, delta 5-dodecadienoyl-CoA, then to trans-2,trans-4-dodecadienoate. The reduction was mediated by 2,4-dienoyl-CoA reductase by the conversion of trans-2,trans-4-dodecadienoyl-CoA into trans-3-dodecenoyl-CoA. However, direct reduction of the cis-5 double bond was also shown to be operating, although to a lesser extent.