title: Peroxisomal degradation of trans-unsaturated fatty acids in the yeast Saccharomyces cerevisiae.
abstract: Degradation of trans-unsaturated fatty acids was studied in the yeast Saccharomyces cerevisiae. Propagation of yeast cells on trans-9 elaidic acid medium resulted in transcriptional up-regulation of the SPS19 gene, whose promoter contains an oleate response element. This up-regulation depended on the Pip2p-Oaf1p transcription factor and was accompanied by induction of import-competent peroxisomes. Utilization of trans fatty acids as a single carbon and energy source was evaluated by monitoring the formation of clear zones 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 isomerase Eci1p. Metabolism of the corresponding even-numbered double bonds proceeded 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-specific 3-hydroxyacyl-CoA dehydrogenase) without the involvement of Sps19p, whereas trans-2,cis-4-dienoyl-CoAs could not. This reductase-independent metabolism of trans-2,trans-4-dienoyl-CoAs resembled the situation postulated for mammalian mitochondria in which oleic acid is degraded through a di-isomerase-dependent pathway. In this hypothetical process, trans-2,trans-4-dienoyl-CoA metabolites are generated by Delta(3)-Delta(2)-enoyl-CoA isomerase and Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase and are degraded by 2-enoyl-CoA hydratase 1 in the absence of 2,4-dienoyl-CoA reductase. Growth of a yeast fox2sps19Delta mutant in which Fox2p was exchanged with rat peroxisomal multifunctional enzyme type 1 on trans-9,trans-12 linolelaidic acid medium gave credence to this theory. We propose an amendment to the current scheme of the carbon flux through beta-oxidation taking into account the dispensability of beta-oxidation auxiliary enzymes for metabolizing trans double bonds at even-numbered positions.
authors.affiliation: Institut für Biochemie und Molekulare Zellbiologie der Universität Wien and Ludwig Boltzmann-Forschungsstelle für Biochemie, Vienna Biocenter, Dr Bohrgasse 9, A-1030 Vienna, Austria. AG@abc.univie.ac.at
authors.forename: A
authors.initials: A
authors.lastname: Gurvitz
authors.forename: B
authors.initials: B
authors.lastname: Hamilton
authors.forename: H
authors.initials: H
authors.lastname: Ruis
authors.forename: A
authors.initials: A
authors.lastname: Hartig
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D019748:Carbon-Carbon Double Bond Isomerases / Q000378:metabolism*; D003001:Cloning, Molecular; D004746:Enoyl-CoA Hydratase / Q000378:metabolism*; D004926:Escherichia coli; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism*; D017930:Genes, Reporter; D005838:Genotype; D007536:Isomerism; D007700:Kinetics; D020675:Peroxisomes / Q000201:enzymology*; D010957:Plasmids; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D005231:Fatty Acids, Unsaturated; D011994:Recombinant Proteins; D004746:Enoyl-CoA Hydratase; C083735:long-chain-enoyl-CoA hydratase; D019748:Carbon-Carbon Double Bond Isomerases; C085575:delta(3,5),delta(2,4)-dienoyl-CoA isomerase