Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 enzymic self-polymerization of prophobilinogen gives rise to the cyclic tetrapyrroles uroporphyrinogen III and uroporphyrinogen I. The former is the precursor of all the natural porphyrins and chlorins. The formation of uroporphyrinogen III is catalysed by a dual enzymic system, porphobilinogen deaminase and uroporphyrinogen III cosynthase. Deaminase polymerizes four porphobilinogen units on the enzymic surface, without liberation of free intermediates into the reaction medium, and forms uroporphyrinogen I. Cosynthase enters into association with the deaminase, and acts as a 'specifier protein' of the latter, changing the mode of porphobilinogen condensation on the enzymic surface. The association is independent of the presence of substrate. While deaminase catalyses the head-to-tail condensation of the porphobilinogen units, the association deaminase-cosynthase catalyses the head-to-head condensation of the same units. As a result different enzyme-bound dipyrrylmethanes are formed form the beginning of the process, and this can be demonstrated by using synthetic dipyrrylmethanes and tripyrranes.
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PMID:Biosynthesis of uroporphyrinogens from porphobilinogen: mechanism and the nature of the process. 0 34

The activities of the enzymes of heme biosynthesis (except protoporphyrin oxidase) have been followed during the induction of Friend cells in culture. All the enzyme activities increased after induction with dimethyl sulfoxide. The activities of the intermediate enzymes were much higher than those of delta-aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37], the initial enzyme, or ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1), the final enzyme of the pathway. Ferrochelatase activity was not detectable in the uninduced cell. delta-Aminolevulinate synthase activity increased during the first 24 hr of induction; porphobilinogen deaminase activity began to increase after 48 hr and ferrochelatase activity, after 72 hr. However, the induction of heme synthesis followed the same time course as that of ferrochelatase activity, not that of delta-aminolevulinate synthase activity. The cellular growth medium was found to contain traces of protoporphyrins. Thus, ferrochelatase is shown to be rate limiting for heme synthesis during early stages of Friend cell induction. A Friend cell variant (Fw), which is not inducible except in the presence of exogenous hemin, was also studied. All the enzymes of heme synthesis except ferrochelatase were inducible by butyric acid. Ferrochelatase was not inducible by butyric acid or hemin plus butyric acid. These cells also excrete protoporphyrin, The failure to induce ferrochelatase activity is believed to be the cause of, not a consequence of, the noninducibility of this cell line.
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PMID:Heme biosynthesis in Friend erythroleukemia cells: control by ferrochelatase. 28 6

In 44 patients with rheumatoid arthritis and 30 control persons, the activities of the following three hemesynthesizing enzymes were determined: delta-aminolevulinic acid dehydratase (D-ALA-D), porphobilinogen deaminase (PBG-D), and ferrochelatase (FCH). Compared with the control persons in patients with rheumatoid arthritis, statistically significant decreased activities of FCH were determined, whereas no differences between the two groups tested occurred with D-ALA-D and PBG-D.
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PMID:[New aspects in the pathogenesis of anemia in chronic polyarthritis]. 29 39

Mutants of Escherichia coli K12 which accumulated the haem precursor porphobilinogen are described. The mutants grew very slowly on carbon and energy sources which K12 uses only oxidatively, and they had low catalase activities, suggesting that they were deficient in haem. Extracts had one-tenth of the parental activity of the enzyme porphobilinogen deaminase. In transduction, the mutation mapped close to genes ilvD and metE at minute 84. The gene was tentatively identified as hemC, coding for porphobilinogen deaminase. The gene symbol hemC replaces the earlier and temporary symbol popE.
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PMID:Mutants of Escherichia coli K12 accumulating porphobilinogen: a new locus, hemC. 37 77

Porphyrin auxotrophs of Bacillus subtilis can be divided into two groups. Strains belonging to the first group (hemA, hemB, or hemC) are not able to synthesize or metabolize porphobilinogen. These strains require cysteine, cystine, and methionine, respectively. Traces of aminolevulinic acid, in a hemin-containing medium, can replace the cysteine requirement in a mutant lacking aminolevulinic acid synthetase. In bacteria belonging to the second group (hemE, hemF, or hemG), porphyrin biosynthesis is blocked at later steps, and the amino acids mentioned above are not required. It is of interest that both the activity of ribonucleotide reductase and the amount of vitamin B12 were significantly lower in the first group. The addition of vitamin B12 to the medium did not promote the growth of strains examined. We assume that porphobilinogen deaminase is essential for the synthesis of corrinoids.
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PMID:Porphyrin and corrinoid mutants of Bacillus subtilis. 40 8

The enzymes of haem biosynthesis have been measured in the peripheral blood of 13 patients with cutaneous hepatic porphyria. The activity of leucocyte delta-aminolaevulinic acid synthase was significantly elevated (p less than 0.001) as was that of erythrocyte porphobilinogen deaminase (p less than 0.05). Leucocyte ferrochelatase activity was depressed (p less than 0.001) and the activity of erythrocyte uroporphyrinogen decarboxylase did not significantly differ from control values. Similar enzyme activities were assayed in 12 chronic alcoholics and 8 patients with liver disease and the results differed markedly from those obtained from the porphyric patients. It is unlikely that the raised leucocyte delta-amino-laevulinic acid synthase activity can be attributed to alcohol ingestion or liver disease. A defect in the activity of uroporphyrinogen decarboxylase may exist in cutaneous hepatic porphyria but this could not be demonstrated in erythrocytes in this study.
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PMID:Haem biosynthesis in cutaneous hepatic porphyria: comparison with alcoholism and liver disease. 46 87

Many hypotheses on uroporphyrinogen biosynthesis advanced the possibility that 2-aminomethyltripyrranes formed by porphobilinogen deaminase are further substrates or uroporphyrinogen III co-synthase in the presence of porphobilinogen. These proposals were put to test by employing synthetic 2-aminomethyltripyrranes formally derived from porphobilinogen. None of them was found to be by itself a substrate of deaminase or of co-synthase in the presence of porphobilinogen. The tripyrranes chemically formed uroporphyrinogens by dimerization reactions, and the latter had to be deducted in control runs during the enzymatic studies. Two of the tripyrranes examined, the 2-aminomethyltripyrrane 7 and the 2-aminomethyltripyrrane 8, were found to be incorporated into enzymatically formed uroporphyrinogen III in the presence of porphobilinogen and of the deaminase-co-synthase system. While the former gave only a slight incorporation, the latter was incorporated in about 16%. No incorporation of 8 into uroporphyrinogen I was detected. On the basis of these results, and of the previous results obtained with 2-aminomethyldipyrrylmethanes, an outline of the most likely pathway of uroporphyrinogen III biosynthesis from porphobilinogen is given.
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PMID:Biosynthesis of uroporphyrinogens. Interaction among 2-aminomethyltripyrranes and the enzymatic system. 61 37

Anemia is a constant complication of uremia. As it has been suggested that uremic toxins (middle molecules) play an important role in the mechanism of anemia, we studied the activities of three heme-synthesizing enzymes: delta-aminolevulinic acid dehydratase, porphobilinogen deaminase and ferrochelatase. In 26 patients on regular dialysis therapy, all three enzymes had significantly lower values than in normal control subjects. From our results, it can be assumed that the decreased heme biosynthesis in chronic uremic patients might be caused by a lack of erythropoietin or by uremic toxins inhibiting erythropoietin and/or heme-synthesizing enzymes.
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PMID:Heme synthesis in anemia of the uremic state. 75 May 46

Hereditary coproporphyria is biochemically distinct from the other porphyrias and is characterized by excessive excretion of coproporphyrin in faeces and usually in urine. The laboratory findings in 28 patients with this disease are presented and the clinical details of eight patients who have been in attack summarised. The remaining 20 patients were latent for the disease. In all patients studied the activity of delta-aminolaevulinic acid synthase was raised and coproporphyrinogen oxidase depressed in the leucocyte. This indicates the partial enzyme block in the haem biosynthetic pathway in this disease. The activities of the other enzymes in the pathway, leucocyte ferrochelatase and erythrocyte delta-aminolaevulinic acid dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase showed no consistent change. On review of 111 cases, 35 per cent presented in acute attack: 80 per cent had abdominal pain, 34 per cent vomiting, 29 per cent solar sensitivity, 23 per cent neurological involvement, 23 per cent psychiatric symptoms and 20 per cent severe constipation. Only two fatalities have been published, both from respiratory failure. There was a female preponderance of cases in attack of 2-5:1 and in the latent cases of 1-5:1 suggesting hormonal provocation in the uncovering of the disease. Drugs were implicated as precipitating 54 per cent of acute attacks and in 34 per cent of cases, these were barbiturates. This study demonstrates the reduction in activity of coproporphyrinogen oxidase in the haem biosynthetic pathway and the elevation of delta-aminolaevulinic acid synthase in the peripheral blood. These features, together with the typical abnormal porphyrin excretion pattern, appear to be diagnostic of hereditary coproporphyria whether in attack, remission, or in the latent form.
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PMID:Hereditary coproporphyria. Demonstration of the abnormalities in haem biosynthesis in peripheral blood. 86 76

1. The activities of the enzymes of haem biosynthesis were studied in 23 patients with acute intermittent porphyria. The mitochondrial enzymes delta-aminolaevulinate synthase, coproporphyrinogen oxidase and ferrochelatase were measured in leucocytes and the cytosolic enzymes delta-aminolaevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase in erythrocytes. 2. Leucocyte delta-aminolaevulinate synthase activity was elevated (P less than 0-001), with marked diminution of porphobilinogen deaminase activity (P less than 0-001) and reduction in the activities of delta-aminolaevulinate dehydratase (P less than 0-01) and uroporphyrinogen decarboxylase (P less than 0-005). 3. A therapeutic regimen based on intravenous laevulose infusion was studied. In four patients in acute attack and one in remission laevulose treatment was associated with a fall in delta-aminolaevulinate synthase activity, a rise in porphobilinogen deaminase and uroporphyrinogen decarboxylase activities, and a fall in urinary prophyrin precursor excretion (P less than 0-001). These studies provide a basis for the evaluation of the use of sugars in acute intermittent porphyria.
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PMID:The treatment of acute intermittent porphyria with laevulose. 91 61


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