Peroxisomal degradation of trans-unsaturated fatty acids in the yeast Saccharomyces cerevisiae

Degradation of trans-unsaturated fatty acids was studied in the yeast Sacch aromyces cerevisiae, Propagation of yeast cells on trans-9 elaidic acid med ium resulted in transcriptional up-regulation of the SPS19 gene, whose prom oter contains an oleate response element. This up-regulation depended on th e Pip2p-Oaf1p transcription factor and was accompanied by induction of impo rt-competent peroxisomes. Utilization of trans fatty acids as a single carb on and energy source was evaluated by monitoring the formation of clear zon es around cell growth on turbid media containing fatty acids dispersed with Tween 80. For metabolizing odd-numbered trans double bonds, cells required the beta -oxidation auxiliary enzyme Delta (3)-Delta (2)-enoyl-CoA isomera se Eci1p, Metabolism of the corresponding even-numbered double bonds procee ded in the absence of Sps19p (2,4-dienoyl-CoA reductase) and Dci1p (Delta ( 3,5)-Delta (2,4)-dienoyl-CoA isomerase). trans-2,trans-4-Dienoyl-CoAs could enter beta -oxidation directly via Fox2p (2-enoyl-CoA hydratase 2 and D-sp ecific 3-hydroxyacyl-CoA dehydrogenase) without the involvement of Sps19p, whereas trans-2,cis-4-dienoyl-CoAs could not. This reductase-independent me tabolism of trans-2,trans-4-dienoyl-CoAs resembled the situation postulated for mammalian mitochondria in which oleic acid is degraded through a di-is omerase-dependent pathway. In this hypothetical process, trans-2,trans-4-di enoyl-CoA metabolites are generated by Delta (3)-Delta (2)-enoyl-CoA isomer ase and Delta (3,5)-Delta (2,4)-dienoyl-CoA isomerase and are degraded by 8 -enoyl-CoA hydratase 1 in the absence of 2,4-dienoyl-CoA reductase. Growth of a yeast fox2sps19 Delta mutant in which Fox2p was exchanged with rat per oxisomal multifunctional enzyme type 1 on trans-9,trans-12 linolelaidic aci d medium gave credence to this theory. We propose an amendment to the curre nt scheme of the carbon flux through beta -oxidation taking into account th e dispensability of beta -oxidation auxiliary enzymes for metabolizing tran s double bonds at even-numbered positions.