Modified uroporphyrinogen decarboxylase activity in a yeast mutant which mimics porphyria cutanea tarda.
The isolation of a new mutant Sm1 strain of yeast, Saccharomyces cerevisiae, is described: this strain was partially defective in haem formation and accumulated large amounts of Zn-porphyrins. Genetic analysis showed that the porphyrin accumulation was under the control of a single nuclear recessive mutation. Biochemical analysis showed that the main porphyrins accumulated in the cells were uroporphyrin and heptacarboxyporphyrin, mostly of the isomer-III type. The excreted porphyrins comprised mainly dehydroisocoproporphyrin. Analysis of uroporphyrinogen decarboxylase activity in the cell-free extract revealed a 70-80% decrease of activity in the mutant and showed that the relative rates of the different decarboxylation steps were modified with the mutant enzyme. A 2-3-fold increase in 5-aminolaevulinate synthase activity was measured in the mutant. The biochemical characteristics of the Sm1 mutant are very similar to those described for porphyria cutanea tarda.
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D009154:Mutation; D011164:Porphyrias / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D012871:Skin Diseases / Q000201:enzymology; D013053:Spectrophotometry; D014575:Uroporphyrinogen Decarboxylase / Q000235:genetics / Q000378:metabolism*
D006418:Heme; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase