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 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

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

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

Heme biosynthetic activity in the symbiotic association involving crithidial flagellates and intracellular bacteroids was studied by enzymic, nutritional, and isotope incorporation experiments. Component organisms and their complexes in this association were analyzed separately to determine the underlying cause of the hemin requirement of hemoflagellates and the role of symbiotes in sparing this requirement of two crithidial species. Nutritional study of symbiote-free flagellates showed that their growth requires at least 0.1 mug/ml of hemin, which can be substituted by protoporphyrin IX, but not by the porphyrin precursors, delta-amino-levulinic acid or porphobilinogen. These flagellates, in the presence of protoporphyrin IX, incorporated 59Fe into heme, indicating that they possess ferrochelatase (EC 4.99.1.1), the terminal enzyme in the heme biosynthetic pathway, which catalyzes the insertion of iron into protoporphyrin IX. In symbiote-containing flagellates serially cultured in a defined medium free of tetrapyrrole compounds, heme and porphyrins can be detected by a fluorophotometric method, indicative of heme biosynthesis. Study of [14C]glycine incorporation into heme showed that the rate is much higher in symbiote-containing flagellates than in those without symbiotes. Microassay of uroporphyrinogen I synthase [EC 4.3.1.8; porphobilinogen ammonia-lyase (polymerizing)] revealed that the specific activity is high in symbiote-containing flagellates and higher still in isolated symbiotes, but essentially negligible in symbiote-free organisms. It is concluded that the bacterial symbiotes augment a very limited heme biosynthetic capacity of host flagellates by supplying uroporphyrinogen I synthase and perhaps other enzymes preceding ferrochelatase in the heme biosynthetic chain.
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PMID:Heme biosynthesis in bacterium-protozoon symbioses: enzymic defects in host hemoflagellates and complemental role of their intracellular symbiotes. 81 Jul 95

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

These studies demonstrate altered activities of renal heme biosynthetic pathway enzymes and elevated levels of urinary uroporphyrin and coproporphyrin in rats during chronic exposure to 3, 5, or 10 ppm methyl mercury hydroxide (MMH). Porphyrinuria appears to occur as a result of inhibition of renal ferrochelatase and uroporphyrinogen I synthetase, with secondary induction of delta-aminolevulinic acid (ALA) synthetase in kidneys but not livers of mercury-exposed rats. Since the renal heme biosynthetic system appears to be highly sensitive to MMH during continuous exposure to levels below those which elicit overt general organ damage, these results may have clinical utility in diagnosing pre-toxic biological responses to mercury in human populations.
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PMID:Renal porphyrinuria during chronic methyl mercury exposure. 88 12

In these studies the effects of ingested arsenic (As(+5)) on hepatic heme biosynthetic capability and hemoprotein function in adult male rats were investigated. Animals exposed for 6 weeks to 0, 20, 40, or 85 ppm sodium arsenate in the drinking water suffered depression of hepatic delta-aminolevulinic acid (ALA) synthetase and heme synthetase (ferrochelatase) activities, with maximal decreases to 67 and 55% of control levels, respectively, at 85 ppm. Concomitantly, urinary uroporphyrin levels were elevated by as much as 12 times, and coproporphyrin by as much as 9 times, control values. The rate of incorporation of (3)H-ALA into mitochondrial and microsomal hemes was depressed by 40-50% at 20 ppm but was increased with regard to controls by as much as 150% at the higher treatment levels. A similar biphasic pattern was observed in regard to (14)C-leucine incorporation into cellular membranal proteins. In contrast, the levels of ALA dehydratase, uroporphyrinogen I synthetase, aminopyrine demethylase, and cytochrome P-450 were not significantly changed in As(+5)-treated rats. These results support the hypothesis that chronic, low level, arsenic exposure results in selective inhibition of mitochondrial-bound heme biosynthetic pathway enzymes (ALA synthetase and heme synthetase) resulting in a substantial increase in urinary porphyrins, uniquely characterized by a greater increase in uroporphyrin than coproporphyrin levels. These changes occur independent of, or prior to, alterations in hepatic hemoprotein-dependent functions and may thus serve in the clinical analysis of pretoxic exposure to arsenic compounds in human populations.
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PMID:Effects of chronic arsenic exposure on hematopoietic function in adult mammalian liver. 90

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

The present study was undertaken to explore the effect of the presence of hepatic tumors induced by diethylinitrosamine (DENA) on the metabolic heme pathway, and to assess whether these tumors can modify the response of rats to the porphyrinogenic drug hexachlorobenzene (HCB) and whether the above mentioned effects occur to a greater extent in females than males. The results obtained showed that: a) Females were more susceptible to the hepatocarcinogenicity of DENA than males. b) Female normal and DENA treated rats were more susceptible than male rats to the porphyrinogenicity of HCB. c) The presence of hepatic DENA induced tumors could diminish basal hepatic ferrochelatase activity. d) Hepatic tumors could modify the response of animals to a porphyrinogenic drug such as HCB. Thus, both female and male DENA/HBC rats accumulated more porphyrins and showed a lower delta-aminolevulinate synthase and uroporphyrinogen I synthase induction than HCB rats. e) The heme pathway was functional in DENA induced tumors in both male and female rats but they were little affected by HCB.
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PMID:Sex comparison of heme pathway in rats bearing hepatic tumors. 178 Oct 34


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