Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.61 (porphobilinogen deaminase)
 637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of acute intermittent porphyria was made in 10 members of a large kindred because of increased excretion of porphobilinogen and delta-aminolevulinic acid in the urine but normal fecal porphyrins. Erythrocyte uroporphyrinogen I synthase activity was normal in all nine subjects in whom it was measured. No hematologic or other cause was found that could secondarily have raised low activity to normal, suggesting that the porphyric subjects may have had no enzyme abnormality in their erythrocytes. On the other hand, in 49 other Finnish patients with acute intermittent porphyria who were unrelated to he kindred, erythrocyte uroporphyrinogen I synthase activity was low. In acute intermittent porphyria there may be two variants, in one of which the enzyme defect is not expressed in the erythrocytes.
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PMID:Normal erythrocyte uroporphyrinogen I synthase in a kindred with acute intermittent porphyria. 725 64

In acute intermittent porphyria (AIP) the inherited metabolic defect residues in a partial enzyme deficiency at the uroporphyrinogen I synthase (URO-S) step of heme biosynthesis. Assay of this enzyme in erythrocytes is increasingly used for diagnosis of the genetic defect. Erythrocyte URO-S activity was measured by three laboratories in members of 14 AIP kindreds and found helpful for diagnosing the asymptomatic carrier state, since activity of the enzyme was usually distributed bimodally. However, a definite diagnosis of the carrier state was not always possible with this assay: approximately 7% of a total of 340 determinations were inconclusive. Repeat enzyme assays, enzyme assays by more than one laboratory, quantitative urine porphobilinogen determinations, and studies of other family members all aided in arriving at a firm diagnosis for most of those in whom a single erythrocyte URO-S measurement was inconclusive. Because the enzyme is unstable, blood specimens should be stored frozen if immediate assay is not possible.
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PMID:The diagnosis of acute intermittent porphyria. Usefulness and limitations of the erythrocyte uroporphyrinogen I synthase assay. 727 Apr 94

The activities of 5 enzymes of the haem biosynthetic pathway and the protoporphyrin concentrations have been measured in peripheral red blood cells of 23 patients having a preleukaemic syndrome with refractory sideroblastic anaemia. A decreased delta-aminolaevulinic acid synthase (ALA-S) activity, an increased uroporphyrinogen I synthase activity and an increased red cell protoporphyrin concentration were consistent findings. Patients with abnormal leucocyte and/or platelet counts in the peripheral blood as well as patients with an excess of blast cells in the bone marrow had the lowest ALA-S activities. A further decrease in ALA-S activity was observed in 3 patients after leukaemic change in the disease. Patients having cytogenetic abnormalities showed no unique enzyme abnormalities. These results indicate that enzymatic disturbances of haem synthesis cannot be used as prognostic indicator of leukaemic transformation in refractory sideroblastic anaemia, but a very low ALA-S activity appears to accompany the development of a leukaemia in such patients.
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PMID:Haem biosynthesis in refractory sideroblastic anaemia associated with the preleukaemic syndrome. 733 57

We describe a convenient, economical procedure for measuring uroporphyrinogen I synthase (EC 4.3 1.8) activity in erythrocytes, the results of which can be used to diagnose acute intermittent porphyria, in either its latent or acute stage. By limiting the test reaction sequence to the conversion of porphobilinogen to porphyrins, we eliminated several disadvantages of alternative methods in which delta-aminolevulinate is used as substrate. The latter assay was inhibited by lead; our procedure was not. Our procedure also gave greater porphyrin synthesis with less substrate. Erythrocytes of healthy women presented a mean activity of 12.4 nmol of porphyrin formed per liter per second; erythrocytes of healthy men presented a mean activity of 11.0 nmol/L per second. The within-run coefficient of variation (CV) for our assay was 1.8%; the between-run CV was 3.1%.
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PMID:Assay for erythrocyte uroporphyrinogen I synthase activity, with porphobilinogen as substrate. 738 90

To obtain some information on porphyrin metabolism in uraemic patients, the activity of erythrocyte uroporphyrinogen I synthetase was measured in patients with chronic renal failure. The results indicate a decreased enzymatic activity which is not due to urea interference, in the hemolysates of these patients.
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PMID:Determination of erythrocyte uroporphyrinogen I synthetase activity in chronic renal failure. 738 35

Problems encountered in the uroporphyrinogen I synthase assay were found to be due to the Triton reagent, slit-width and excitation wavelength settings of the spectrophotofluorometer, and leg-phase in the enzyme reaction. Of Triton X-100 from four suppliers, only three were found suitable. Differences in enzyme activity owing to slit-width adjustments were resolved by measuring the fluorescence of the sample (uroporphyrin) at 405 nm and the standard (coproporphyrin) at 401 nm. The lag-phase in the activated-enzyme assay is incorporated in the 30-min preincubation of the blood specimen in our modified method, thus giving higher enzyme activity than found with the original assay. The range for our method is 7.3--15.8 nmol s-1 L-1 (mean = 10.9; SD = 2.07).
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PMID:Reappraisal of the uroporphyrinogen I synthase assay, and a proposed modified method. 739 50

Fifty-seven patients with variegate porphyria belonging to nine families are described. The prevalence of variegate porphyria in Finland is 1.3 per 100 000. Eighteen patients had had acute attacks. During on average 5.7 years' follow-up only two of 48 patients had symptoms, which were temporary and acute. The length of life of 13 genealogically traced gene carriers who lived mostly during the 19th century did not differ from that of the general population. Skin fragility occurred in 45 per cent of the patients and was usually mild. No patients were sensitive to sunlight but seven of 14 tested reacted abnormally to artificial light. The characteristic increase in the excretion of faecal proto- and coproporphyrin was usually apparent even in the latent stage of porphyria, but increased excretion of urinary porphyrin precursors occurred only during an acute attack. However, in seven of 48 patients studied during the latent stage, faecal prophyrins were only slightly elevated or even normal, causing problems in diagnosis. Determination of faecal X-porphyrin was of no help in diagnosis. Red cell free protoporphyrin was significantly higher and serum haemopexin lower than in controls. Red cell uroporphyrinogen I synthase activity was normal in 17 of 18 patients studied. We conclude that variegate porphyria may be commoner than hiherto suspected; only half the patients in temperaure and cold climates have skin symptoms, the risk of developing an acute attack is low, and some adult patients excrete normal or only slightly abnormal amounts of porphyrin.
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PMID:Variegate porphyria. Twelve years' experience in Finland. 743 35

A new form of acute hepatic porphyria with double genetic defect--deficiency of porphobilinogen deaminase and coproporphyrinogen oxidase--is described. Among 17 studied family members this double enzymatic deficiency was found in five individuals, deficiency of porphobilinogen deaminase in four, and deficiency of coproporphyrinogen oxidase in two. Only the proband had an attack of porphyria. Apart from the proband, all family members had normal urinary PBG excretion. Increased faecal coproporphyrin excretion was found in three people. The results obtained suggest that deficiency of porphobilinogen deaminase and coproporphyrinogen oxidase can be inherited independently. coproporphyrinogen oxidase can be inherited independently.
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PMID:Coexistence of hereditary coproporphyria with acute intermittent porphyria. 802 30

The human histone H2A.X gene is unusual in that its transcripts are alternatively processed to yield two species, one a 0.6-kb replication-linked histone mRNA and the other a 1.6-kb polyadenylated mRNA. The H2A.X gene has been localized by fluorescence in situ hybridization to chromosome 11q23.2-q23.3, away from the known clusters of human histone genes on chromosomes 1, 6, and 12. Assignment to chromosome 11 was substantiated by analysis of human-hamster somatic cell hybrid lines. As this work was being completed, an 89-bps sequence overlap was found between the downstream regions of the H2A.X gene and the recently sequenced hydroxymethylbilane (HMB)-synthase gene. The H2A.X and HMB-synthase genes have an unusual arrangement, being transcribed towards each other with their polyadenylation sites 330 bp apart. In addition the HMB-synthase gene contains constitutive and erythroid specific promoters. K562, an erythroid cell line, was found to contain a high concentration of the 1.6-kb polyadenylated H2A.X mRNA.
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PMID:Chromosomal localization of the human histone H2A.X gene to 11q23.2-q23.3 by fluorescence in situ hybridization. 807 49

The study was aimed to assess the protective efficacy of zinc against hemo and hematotoxicity induced by lead. Two groups of 8 rats each, were administered lead acetate 20 mg/kg bw (ip) for 3 days. One group in addition was injected 5 mg/kg bw (ip) zinc acetate for next three days. A third group of 8 rats was given three injections of normal saline and served as control. All the animals were sacrificed on eighth day and assessed for hematological changes, heme synthesizing pathway enzymes, hepatic drug metabolizing status and sulfhydryl levels in blood and liver. Lead administration resulted in decreased hemoglobin, increased reticulocytosis, depression of delta aminolevulinic acid dehydratase (ALAD) and uroporphyrinogen I synthetase (UPS) activity in blood and liver. In vitro metabolism of drugs aminopyrine, aniline and p-nitroanisole by liver homogenate and in vivo metabolism of pentabarbitone was also reduced in lead exposed rate. Zinc treated rats showed improved hematological profile and activated ALAD and UPS activity, recovery of N-demethylation of aminopyrine and O-demethylation of p-nitroanisole and partial restoration of free thiol levels in blood and liver thereby indicating that zinc could confer protection against lead toxicity.
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PMID:Preventive action of zinc against lead toxicity. 858 50


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