scholarly journals Modified uroporphyrinogen decarboxylase activity in a yeast mutant which mimics porphyria cutanea tarda

1984 ◽  
Vol 218 (2) ◽  
pp. 405-413 ◽  
Author(s):  
J Rytka ◽  
T Bilinski ◽  
R Labbe-Bois
Keyword(s):  
Biochemical Analysis ◽  
Porphyria Cutanea Tarda ◽  
Fold Increase ◽  
Recessive Mutation ◽  
Decarboxylase Activity ◽  
Cell Free Extract ◽  
Yeast Mutant ◽  
Uroporphyrinogen Decarboxylase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Biochemical Characteristics

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.

scholarly journals The effects in vivo of mutationally modified uroporphyrinogen decarboxylase in different hem12 mutants of baker's yeast (Saccharomyces cerevisiae)

1988 ◽  
Vol 253 (1) ◽  
pp. 109-116 ◽  
Author(s):  
A Kurlandzka ◽  
T Zoladek ◽  
J Rytka ◽  
R Labbe-Bois ◽  
D Urban-Grimal
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Porphyria Cutanea Tarda ◽  
Baker’S Yeast ◽  
Decarboxylase Activity ◽  
Baker's Yeast ◽  
Uroporphyrinogen Decarboxylase ◽  
Human Form ◽  
Yeast Saccharomyces Cerevisiae ◽  
Diploid Cells

Nine new hem12 haploid mutants of baker's yeast (Saccharomyces cerevisiae), totally or partially deficient in uroporphyrinogen decarboxylase activity, were subjected to both genetic and biochemical analysis. The mutations sites studied are situated far apart within the HEM12 gene located on chromosome IV. Uroporphyrinogen decarboxylase activity in the cell-free extracts of the mutants was decreased by 50-100%. This correlated well with the decrease of haem formation and the increased accumulation and excretion of porphyrins observed in vivo. The pattern of porphyrins (uroporphyrin and its decarboxylation products) accumulated in the cells of mutants partially deficient in uroporphyrinogen decarboxylase activity did not differ significantly, although differences in vitro were found in the relative activity of the mutant enzyme at the four decarboxylation steps. The excreted porphyrins comprised mainly dehydroisocoproporphyrin or pentacarboxyporphyrin. In heterozygous hem12-1/HEM12 diploid cells, a 50% decrease in decarboxylase activity led to an increased accumulation of porphyrins as compared with the wild-type HEM12/HEM12 diploid, which points to the semi-dominant character of the hem12-1 mutation. The biochemical phenotypes of both the haploid and the heterozygous diploid resembles closely the situation encountered in porphyria cutanea tarda, the most common human form of porphyria.

scholarly journals Hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients: The influence of virus C infection

Hepatology ◽  
1998 ◽  
Vol 27 (2) ◽  
pp. 584-589 ◽  
Author(s):  
Maria Jose Moran ◽  
Antonio Fontanellas ◽  
Eric Brudieux ◽  
Isabelle Hombrados ◽  
Victor de Ledinghen ◽  
...  
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase ◽  
Virus C

Identification of Two Types of Porphyria Cutanea Tarda by Measurement of Erythrocyte Uroporphyrinogen Decarboxylase

1980 ◽  
Vol 58 (6) ◽  
pp. 477-484 ◽  
Author(s):  
G. H. Elder ◽  
Diane M. Sheppard ◽  
R. E. De Salamanca ◽  
A. Olmos
Keyword(s):  
Family History ◽  
Autosomal Dominant ◽  
Porphyria Cutanea Tarda ◽  
Dominant Gene ◽  
Decarboxylase Activity ◽  
Hepatic Enzyme ◽  
Uroporphyrinogen Decarboxylase ◽  
History Of ◽  
The Common ◽  
Dominant Characteristic

1. Erythrocyte uroporphyrinogen decarboxylase activity has been measured in 27 patients with porphyria cutanea tarda, of whom 11 had a family history of overt porphyria cutanea tarda. 2. Eight patients from six families had erythrocyte uroporphyrinogen decarboxylase activities that were decreased to about half of control values. This decrease was shown by family studies to be inherited as an autosomal dominant characteristic. Two of these patients had no family history of overt porphyria cutanea tarda. 3. Nineteen patients had uroporphyrinogen decarboxylase activities close to or within the range found in 18 control subjects. Of these, five patients had a family history of porphyria cutanea tarda. 4. Inheritance of an autosomal dominant gene which decreases uroporphyrinogen decarboxylase activity in erythrocytes and liver is an uncommon cause of porphyria cutanea tarda and may not explain all cases of familial porphyria cutanea tarda. The hepatic enzyme defect in the common type of porphyria cutanea tarda, in which erythrocyte uroporphyrinogen decarboxylase activity is normal, may be caused either by inheritance of a gene whose effect is restricted to the liver or by chemicals that selectively inhibit the hepatic enzyme.

scholarly journals Identification of amino acid changes affecting yeast uroporphyrinogen decarboxylase activity by sequence analysis of hem12 mutant alleles

1992 ◽  
Vol 288 (3) ◽  
pp. 753-757 ◽  
Author(s):  
A Chelstowska ◽  
T Zoladek ◽  
J Garey ◽  
J Kushner ◽  
J Rytka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Point Mutations ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Active Centre ◽  
Nonsense Mutations ◽  
Mutant Strains ◽  
Leaky Mutants

The molecular basis of the uroporphyrinogen decarboxylase defect in eleven yeast ‘uroporphyric’ mutants was investigated. Uroporphyrinogen decarboxylase, an enzyme of the haem-biosynthetic pathway, catalyses the decarboxylation of uroporphyrinogen to coproporphyrinogen and is encoded by the HEM12 gene in the yeast Saccharomyces cerevisiae. The mutations were identified by sequencing the mutant hem12 alleles amplified in vitro from genomic DNA extracted from the mutant strains. Four mutations leading to the absence of enzyme protein were found: one mutation caused the substitution of the translation initiator Met to Ile, a two-base deletion created a frameshift at codon 247 and two nonsense mutations were found at codons 50 and 263. Four different point mutations were identified in seven ‘leaky’ mutants with residual modified uroporphyrinogen decarboxylase activity; each of three mutations was found in two independently isolated mutants. The nucleotide transitions resulted in the amino acid substitutions Ser-59 to Phe, Thr-62 to Ile, Leu-107 to Ser, or Ser-215 to Asn, all located in or near highly conserved regions. The results suggest that there is a single active centre in uroporphyrinogen decarboxylase, the geometry of which is affected in the mutant enzymes.

scholarly journals Effects of polychlorinated biphenyl compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic uroporphyrinogen decarboxylase. Implications for the pathogenesis of porphyria

1983 ◽  
Vol 214 (1) ◽  
pp. 145-151 ◽  
Author(s):  
H De Verneuil ◽  
S Sassa ◽  
A Kappas
Keyword(s):  
Polychlorinated Biphenyl ◽  
Porphyria Cutanea Tarda ◽  
Metabolic Activation ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase ◽  
Simultaneous Treatment ◽  
Synergistic Response ◽  
Low Levels ◽  
Tetrachlorodibenzo P Dioxin

Treatment of cultured chick embryo hepatocytes with phenobarbital, polychlorinated biphenyl compounds and 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in increased delta-aminolaevulinate synthase and decreased uroporphyrinogen decarboxylase activities and porphyrin accumulation; uroporphyrin and heptacarboxyporphyrin predominated. Iron had no effect on these changes. Simultaneous treatment of cultures with dioxin and phenobarbital produced a synergistic response in delta-aminolaevulinate synthase induction, uroporphyrinogen decarboxylase inhibition and porphyrin accumulation. These data suggest that an inhibitor of uroporphyrinogen decarboxylase may be generated in the liver from polychlorinated biphenyl compounds or dioxin by metabolic activation. Additionally these findings bear on the postulated role of these and related chemicals in determining the low levels of uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients.

Decreased Hepatic Uroporphyrinogen Decarboxylase Activity in Porphyria Cutanea Tarda

1982 ◽  
Vol 306 (13) ◽  
pp. 766-769 ◽  
Author(s):  
Bertram F. Felsher ◽  
Noemi M. Carpio ◽  
David W. Engleking ◽  
Allan T. Nunn
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase
Sign in / Sign up

Export Citation Format

Share Document