Changing stereochemistry for a metabolic pathway in vivo. Experiments with the peroxisomal beta-oxidation in yeast.
The biosphere is inherently built of chiral molecules, and once their metabolism is established, the stereochemical course of the reactions involved is seen to remain highly conserved. However, by replacing the yeast peroxisomal multifunctional enzyme (MFE), which catalyzes the second and third reactions of beta-oxidation of fatty acids via D-3-hydroxyacyl-CoA intermediates, with rat peroxisomal MFE, which catalyzes the same reactions via L-3-hydroxy intermediates, it was possible to change the chiralities of the intermediates in a major metabolic pathway in vivo. Both stereochemical alternatives allowed the yeast cells to grow on oleic acid, implying that when the beta-oxidation pathways evolved, the overall function was the determining factor for the acquisition of MFEs and not the stereospecificities of the reactions themselves.
D015094:3-Hydroxyacyl CoA Dehydrogenases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004746:Enoyl-CoA Hydratase; D005816:Genetic Complementation Test; D007535:Isomerases; D007700:Kinetics; D008830:Microbodies / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D010084:Oxidation-Reduction; D063994:Peroxisomal Bifunctional Enzyme; D010957:Plasmids; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
D009097:Multienzyme Complexes; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases