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

---

Query: EC:2.5.1.61 (porphobilinogen deaminase)
637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene lesion of the porphyrin-heme synthetic pathway in acute intermittent porphyria (AIP) is reflected in a deficient level of activity of the cytosol enzyme uroporphyrinogen I synthetase (URO-S). A marked URO-S deficiency has been demonstrated in the liver and in circulating erythrocytes of individuals with both active and latent AIP. This enzymic abnormality accounts for the excessive production and excretion into urine of the porphyrin precursors, lamda-aminolevulinic acid (ALA) and porphobilinogen (PBG) in AIP subjects. In this study, utilizing cell culture techniques, a marked URO-S deficiency has also been demonstrated in skin fibroblasts from AIP patients and in cells derived through aminocentesis from an approximately 17-wk old fetus. The prenatal diagnosis of the AIP trait in this fetus was confirmed postnatally by the demonstration in the child of a deficient level of erythrocyte URO-S activity which was comparable to those found in her AIP mother and affected sibling and which was approximately one-half the levels characterizing her normal father and aunt and a second unaffected sibling. The identification of the URO-S deficiency in cultured human fibroblasts from AIP patients was facilitated by a newly developed, sensitive assay for the enzyme activity. In this assay, the ability of such cells to convert ALA to protoporphyrin was quantitated; in the sequence of reactions involved in this transformation, URO-S is limiting so that the gene defect of AIP could be simply and precisely determined by appropriate spectrofluorometry of cell extracts. The technique described has distinct advantages over the direct enzymatic assay for URO-S activity in cultured human skin fibroblasts and permits clear differentiation of AIP carrier from normal individuals.
...
PMID:Studies in porphyria. IV. Expression of the gene defect of acute intermittent porphyria in cultured human skin fibroblasts and amniotic cells: prenatal diagnosis of the porphyric trait. 116 72

The activities of 5-aminolaevulinate dehydrase (ALA-D), hydroxymethylbilane synthase (HMB-S), uroporphyrinogen III synthase (URO-S) and uroporphyrinogen decarboxylase (URO-D) in the erythrocytes of alcoholics were assayed and compared with those in controls and abstaining alcoholics. The HMB-S and URO-S activities in alcoholics were significantly higher than the controls and there were significant correlations between enzyme activities and mean corpuscular volume (MCV). Alcoholics abstaining from alcohol over a nine-month period showed a return to normal enzyme activities in parallel with the normalization of their MCV. Abstaining alcoholics thus all had normal HMB-S and URO-S activities. The ALA-D and URO-D activities of alcoholics were not significantly different from controls or from abstaining alcoholics. Alcohol appears to have a selective effect on the haem biosynthetic enzymes in the erythron.
...
PMID:High performance liquid chromatographic studies of erythrocytes haem biosynthetic enzyme activities in alcoholic macrocytosis. 228 50

Rhodopseudomonas palustris uroporphyrinogen I synthetase (URO-S) has been chemically attached to Sepharose 4B and some of its properties have been studied. When 7-8 mg protein/ml activated Sepharose was used, immobilized URO-S retained 45% of the activity of the original soluble preparation, with a coupling yield of 66% after a period of 15 h. Optimal incubation conditions for the activity of gel-enzyme were determined. Unlike the soluble enzyme, the Sepharose-bound URO-S showed a biphasic substrate saturation curve, indicating that a protein conformational change had occurred during the process of immobilization. Immobilized URO-S stored at 4 degrees C for 35 days retained 90% of activity and when repeatedly used, up to 5 times, retained 48% of the original activity. Attachment of URO-S to Sepharose led to an enhanced thermal stability.
...
PMID:Immobilized uroporphyrinogen I synthetase from Rhodopseudomonas palustris. 236 Sep 91

Carbamazepine (CBMZP) has been implicated as an inhibitor of the activities of 5-aminolaevulinic acid dehydratase (ALA-D) and uroporphyrinogen I synthetase (URO-S). In an epileptic boy undergoing long-term treatment with valproic acid (VPA), 1.3 g/d, CBMZP, 0.9 g/d and folic acid, 7.5 mg/d, decreased activities of ALA-D and URO-S coincided with increased levels of erythrocyte protoporphyrin (EP) in the absence of Pb poisoning, iron depletion and erythropoietic protoporphyria. A progressive fall in plasma pyridoxal 5'-phosphate (B6-P) to 7.7 nmol/L (lower reference limit, 14.6 nmol/L) prompted implementation of pyridoxine HCl (B6-HCl), 87.5 mg/d followed by administration of both B6-HCl and preformed B6-P (50 mg/d each). This permitted the eventual withdrawal of VPA and a net reduction of CBMZP to 450 mg/d. During these manipulations, ALA-D and URO-S activities, EP and urinary porphyrins and their precursors were measured serially. An assay system utilizing red cell ALA-D for generation of porphobilinogen (PBG) from added ALA at pH 7.4 was used for determination of ALA-D and URO-S activities in separate aliquots of the same assay mixture both in the absence and presence of Zn and dithiothreitol (DTT). One unit (U) for ALA-D = 1 nmol PBG/L RBC/s; for URO-S = 1 nmol porphyrin/L/s; minimum normal level for ALA-D = 135 U; for URO-S = 6 U. B6-HCl alone entailed increases in ALA-D and URO-S prior to any reduction of CBMZP. After administration of both B6-HCl and B6-P and withdrawal of VPA, the overall increase in ALA-D was from 54.59 to 197.2 U (-Zn; -DTT) and from 50.76 to 217.3 U (+Zn; +DTT). The overall increase in URO-S was from 2.67 to 8.90 U (-Zn; -DTT) and from 3.02 to 8.66 U (+Zn; +DTT). During stepwise reduction of VPA, EP remained elevated to values as high as 2.48 mumol/L (upper reference limit, 1.33 mumol/L). Only after permanent withdrawal of VPA did concentrations of EP fall to normal levels. Values for porphyrins and their precursors in urine were normal throughout. Since both VPA and B6-P are strongly protein-bound, it is suggested that VPA displaced B6-P from protective protein binding sites and that the resulting deficit in B6-P (rather than CBMZP) reduced ALA-D and URO-S activities via primary reduction of ALA-synthetase activity. Increases in EP emerge as a hitherto unappreciated effect of VPA warranting further investigation.
...
PMID:Protoporphyrinaemia and decreased activities of 5-aminolevulinic acid dehydrase and uroporphyrinogen I synthetase in erythrocytes of a Vitamin B6-deficient epileptic boy given valproic acid and carbamazepine. 250 Feb 71

The pre-clinical diagnosis of acute intermittent porphyria (AIP) is important because acute attacks can be brought about by drugs, liver toxins, hormonal changes and diet. There also may be no obvious precipitating agent. The discovery that the activity of uroporphyrinogen I synthase (URO-S) activity in the red blood cells of patients with AIP is half that found in normal persons is of great value in diagnosing this disorder and also appears useful in detecting patients with the latent disease who have normal urinary delta-aminolevulinic acid and porphobilinogen excretion. It also appears to distinguish other types of porphyria from acute intermittent porphyria. It must also be recognized that some red blood cells URO-S determinations will yield indeterminate results; therefore, repeat assays, including examination of kinship, will improve discrimination and confidence in the final diagnosis.
...
PMID:Erythrocyte uroporphyrinogen I synthase activity as an indicator of acute porphyria. 275 Dec 41

Rapid and reproducible assays for uroporphyrinogen III synthase (URO-S; EC 4.2.1.75) have been developed and used to determine the enzymatic activity in human erythrocytes and cultured lymphoid cells. In the coupled-enzyme assay, porphobilinogen was first converted to hydroxymethylbilane, the natural substrate for URO-S, by hydroxymethylbilane synthase which was conveniently obtained from heat-treated erythrocyte lysates. In the direct assay, synthetic hydroxymethylbilane was used as substrate. In both assays, the uroporphyrinogen reaction products were oxidized to their respective uroporphyrin isomers, which were then resolved and quantitated by reversed-phase high-pressure liquid chromatography. Both assays were optimized for pH, substrate concentration, and linearity with time and protein concentration. The mean URO-S activities in normal human erythrocyte lysates determined by the coupled-enzyme and direct assays were 7.41 +/- 1.35 and 7.64 +/- 1.73 units/mg protein, respectively. In normal human cultured lymphoid cells, the mean activities were 13.7 +/- 1.39 and 17.6 +/- 1.15 units/mg protein for the coupled-enzyme and direct assays, respectively. In four families with congenital erythropoietic porphyria, both assays reliably identified the markedly decreased URO-S activities in erythrocytes and cultured lymphoid cells from affected homozygotes and the half-normal activities in these sources from obligate heterozygotes. The coupled-enzyme assay was easier to perform and was suited for clinical diagnostic assays and for monitoring enzyme purification procedures, while the direct assay, which required substrate preparation and technical dexterity, was best for kinetic studies of URO-S.
...
PMID:Coupled-enzyme and direct assays for uroporphyrinogen III synthase activity in human erythrocytes and cultured lymphoblasts. Enzymatic diagnosis of heterozygotes and homozygotes with congenital erythropoietic porphyria. 367 3

The activity of lymphocyte uroporphyrinogen synthase (URO-S) was examined in 51 non-Hodgkin's lymphoma (NHL) patients at various follow-up periods. Mean +/- SD activity (pmol porphyrin/mg protein/hr) at diagnosis (n = 24), on relapse (n = 14) and during active disease (n = 14) were 31.7 +/- 19.8, 31.7 +/- 27.2 and 29.4 +/- 18.5, respectively. These values were significantly higher than the enzyme activity during remission (14.1 +/- 4.0), which was in the normal range (14.5 +/- 3.8). Abnormally high activity was found in 65.4% of determinations at diagnosis, on relapse and during active disease, compared to 5.5% during remission (P less than 0.001). Significant association of abnormal URO-S activity was found with advanced clinical stage (P less than 0.01), spleen enlargement (P = 0.048), involvement of bone marrow (P = 0.02), as well as lymphoma cell spread to peripheral blood (P = 0.03). Highly significant correlation (r = 0.65, P less than 0.001) was found between URO-S activity and serum lactic dehydrogenase (LDH) levels. Excessively high levels of URO-S activity were found only in patients with lymphoma cells in peripheral blood. No association was found with histopathologic classification and liver size. The authors conclude that URO-S activity is a biochemical indicator for patients in all stages of NHL and seems to be a specific marker for the extensiveness of the disease.
...
PMID:Lymphocyte urosynthase in non-Hodgkin's lymphoma. An indicator of disease extensiveness. 379 Nov 49

An autopsy case of a 37-year-old woman with acute porphyria is reported. The patient began to complain of severe menstrual pains, and later developed serious peripheral neuropathy and various autonomic nervous symptoms. The autopsy revealed a marked loss and degeneration of axons and myelin sheaths in the peripheral nervous system (PNS), and prominent central chromatolysis of the spinal anterior horn cells. The predominant process of the peripheral neuropathy appeared to be axonal degeneration. Biochemical analysis showed a marked increase of delta-aminolevulinic acid (ALA), porphobilinogen, uroporphyrin, and coproporphyrin in the urine, and an increase of coproporphyrin and protoporphyrin in the stools and blood. In the analysis of the enzymatic activities of the liver and bone narrow, the activity of ALA synthetase (ALA-S) was markedly increased, and the activities of both uroporphyrinogen I synthetase (URO-S) and ferrochelatase were decreased. It was characteristic in this case that the enzymatic abnormalities found in both acute intermittent porphyria (AIP) and variegate porphyria (VP) coexisted. Biochemical analysis of the sciatic nerve showed an increase of ALA-S activity and a decrease of both URO-S and ALA dehydrase activities. This was the first report that indicated the presence of abnormal activities of the heme biosynthetic enzymes in the peripheral nerves of porphyric patients. The possibility was discussed that these enzymatic abnormalities of the heme biosynthesis in the peripheral nerve itself might be strongly related to the pathogenesis of the porphyric neuropathy.
...
PMID:An autopsy case of acute porphyria with a decrease of both uroporphyrinogen I synthetase and ferrochelatase activities. 608 95

Acute intermittent porphyria has hitherto been recognised as an autosomal dominant inborn error of haem metabolism characterised by a depressed activity of the enzyme uroporphyrinogen I synthase (URO.S). A case of non-hereditary acute porphyria, similar to acute intermittent porphyria, following treatment of epilepsy with carbamazepine is reported. Subsequent measurements of erythrocyte URO.S activity in a group of epileptic patients treated with various combinations of anticonvulsant drugs suggest that carbamazepine exerts a direct suppressant effect on URO.S in addition to its indirect enzyme-inducing properties.
...
PMID:Carbamazepine-induced non-hereditary acute porphyria. 613 32

Patients with active lymphoproliferative diseases were shown to have high activity of erythrocyte uroporphyrinogen synthetase (URO-S), the enzyme which converts porphobilinogen to uroporphyrinogen. In a few patients examined the lymphocyte URO-S was markedly increased. No correlation was found between the high URO-S activity and the degree of anemia, reticulocytosis, or the presence of hemolysis. Patients with epithelial malignancies and with some common viral diseases had normal erythrocyte URO-S values. Three patients with nonalcoholic cirrhosis also had high erythrocyte URO-S activities. The determination of erythrocyte and lymphocyte URO-S activity may be of aid in the diagnosis of lymphoproliferative diseases. It may also indicate whether remission has been achieved and whether treatment should be continued or reinstituted. These preliminary observations justify the investigation of a larger patient and control material.
...
PMID:Erythrocyte uroporphyrinogen synthase activity as a possible diagnostic aid in the diagnosis of lymphoproliferative diseases. 687 24


1 2 Next >>

---