Abstract
In Saccharomyces cerevisiae the metabolic degradation of saturated fatty acids is exclusively confined to peroxisomes. In addition to a functional beta-oxidation system, the degradation of unsaturated fatty acids requires auxiliary enzymes, including a Delta2, Delta3-enoyl-CoA isomerase and an NADPH-dependent 2,4-dienoyl-CoA reductase. We found both enzymes to be present in yeast peroxisomes. The impermeability of the peroxisomal membrane for pyrimidine nucleotides led to the question of how the NADPH needed by the reductase is regenerated in the peroxisomal lumen. We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. The newly identified peroxisomal protein is homologous to the mitochondrial Idp1p and cytosolic Idp2p, which both are yeast NADP-dependent isocitrate dehydrogenases. Yeast cells lacking Idp3p grow normally on saturated fatty acids, but growth is impaired on unsaturated fatty acids, indicating that the peroxisomal Idp3p is involved in their metabolic utilization. The data presented are consistent with the assumption that peroxisomes of S. cerevisiae contain the enzyme equipment needed for the degradation of unsaturated fatty acids, including an NADP-dependent isocitrate dehydrogenase, a putative constituent of a peroxisomal NADPH-regenerating redox system.
Highlights
A typical metabolic pathway of peroxisomes is the -oxidation of fatty acids [5, 6]
Yeast Peroxisomes Contain Auxiliary Enzymes Needed for the Degradation of Unsaturated Fatty Acids—The ability of S. cerevisiae to grow on unsaturated fatty acids as the single carbon source (Fig. 11), the presence of an NADP-dependent isocitrate dehydrogenase in peroxisomes (Fig. 6), and its suggested role of supplying NADPH for the degradation of unsaturated fatty acids encouraged us to search for auxiliary enzymes of this pathway
In line with a role in the peroxisomal metabolism of unsaturated fatty acids, the Idp3p has been demonstrated to be exclusively peroxisomal, and the protein was shown to be essential for the growth of S. cerevisiae on unsaturated fatty acids but dispensable for growth on saturated fatty acids
Summary
A typical metabolic pathway of peroxisomes is the -oxidation of fatty acids [5, 6]. whereas the presence of a mitochondrial -oxidation system is restricted to mammalian cells and a few protists [7], the fatty acid oxidation in peroxisomes is nearly ubiquitous among eukaryotic cells [7, 8]. Subsequent sucrose density gradient fractionation confirmed the absence of the mitochondrial enzyme and demonstrated the activity to exclusively co-segregate with peroxisomal marker enzymes (Fig. 6), consistent with the presence of a peroxisomal isoenzyme of the NADP-dependent isocitrate dehydrogenases in S. cerevisiae.
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