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)

Uroporphyrinogen III synthase (hydroxymethylbilane hydro-lyase (cyclizing); EC 4.2.1.75), the fourth enzyme in the heme biosynthetic pathway, was purified to homogeneity from human erythrocytes. For enzyme purification and characterization, a sensitive coupled enzyme assay was used which generated the substrate, hydroxymethylbilane; the oxidized product, uroporphyrin III, was quantitated by high pressure liquid chromatography. Uroporphyrinogen III synthase was initially separated from delta-aminolevulinate dehydratase and hydroxymethylbilane synthase by a preparative anion exchange chromatographic step. Subsequent chromatography on hydroxyapatite, phenyl-Sepharose, and Sephadex G-100 purified the enzyme about 70,000-fold with an 8% yield. Homogeneous enzyme was obtained following a final C4-reversed phase high pressure liquid chromatographic step which removed a single major and several minor protein contaminants from the enzyme. The purified enzyme had a specific activity of over 300,000 units/mg, an isoelectric point of 5.5, and was thermolabile (t1/2 at 60 degrees C approximately 1 min). Molecular weight studies by gel filtration (Mr approximately equal to 30,000) and analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr approximately equal to 29,500) were consistent with the enzyme being a monomer. Using hydroxymethylbilane as substrate, the purified enzyme formed uroporphyrinogen III in the absence of hydroxymethylbilane synthase or other cofactors. The pH optimum was 7.4 and the Km for hydroxymethylbilane was 5-20 microM. The enzyme was activated by Na+, K+, Mg+, and Ca2+ and was inhibited by Cd2+, Cu2+, Hg2+, and Zn2+. Amino acid composition analysis was performed, and the N-terminal sequence, Met-Lys-Val-Leu-Leu-Leu, was determined by microsequencing. The availability of the purified enzyme should permit investigation of its reaction mechanism as well as facilitate biochemical and molecular studies of the genetic defect in congenital erythropoietic porphyria.
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PMID:Purification and properties of uroporphyrinogen III synthase from human erythrocytes. 380 19

The lymphocyte transformation test and the macrophage migration inhibition test are quantitative methods invaluable for examination of beryllium (hereafter referred to as Be) effects on cell-mediated immunity. We recognized that the Be sensitizing ability was related to active as well as passive cell-mediated immunity in mice subcutaneously injected with Be once a week over a 6-week period. Be also affects B cells, and it increases the amount of immunoglobulins in sera. In the study of immunological health surveys of Be workers in a copper-beryllium casting factory, the serum complement titer tended to be lower in Be workers than in the controls. In mice, injected with Be once a week over a 12-week period, serum complement titers decreased. Correlation coefficients of the experimental parameters showed a significant negative correlation between the complement titers and the prothrombin time or the coagulation time for factor VII, using mice injected with 5 micrograms of Be. It was suggested that increases in the complement titers after Be administration may be induced by temporarily-activated plasma serin protease, which is a component of blood coagulation factor VII. The delta-aminolevulinic acid dehydratase and porphobilinogen deaminase activities were significantly elevated in the pregnant untreated group, compared with the nonpregnant mice (the control group). However, it was noted that these values in the pregnant mice injected with 50 micrograms of Be were almost the same as the values of the controls. It suggests that Be suppressed the expected pregnancy-induced increase in hematopoietic function. There are at least two risk factors induced in the effects of beryllium on organisms-exposure to the metal and inheritance of the genetic marker. It is necessary to reduce exposure, to give preventive education and to carry out periodic health examinations for the prevention of disease induced by Be.
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PMID:[Immunotoxicity of beryllium]. 952 58