Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selected aspects of the metabolism of Plasmodium falciparum are reviewed, but conclusions based on the study of other species of plasmodia are intentionally not included since these may not be applicable. The parasites increase glucose consumption 50-100 fold as compared to uninfected red cells; most of the glucose is metabolized to lactic acid. The parasite contains a complete set of glycolytic enzymes. Some enzymes such a hexokinase, enolase and pyruvate kinase are vastly increased over corresponding levels in uninfected red cells. However, the pathway for synthesizing 2,3-diphosphoglycerate (2,3-DPG) is absent. Parasitized red cells show a decline in the concentration of 2,3-DPG which may function as an inhibitor for certain essential enzyme pathways. Pentose shunt activity is increased in absolute terms, but as a percent of total glucose consumption, there is a decrease during parasite infection of the red cell. The parasite contains a gene for G6PD and can produce a small quantity of parasite-encoded enzyme. It is not clear if the production of this enzyme can be up-regulated in G6PG deficient host red cells. The NADPH normally produced by the pentose shunt can be obtained from other parasite pathways (such as glutamate dehydrogenase). NADPH may subserve additional needs in the infected red cell such as driving diribonucleotide reductase activity--a rate limiting enzyme in DNA synthesis. The role of NADPH in protecting the parasite-red cell system against oxidative stress (via glutathione reduction) remains controversial. Parasitized red cells contain about 10 times more NAD(H) than uninfected red cells, but the NADP(H) content is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasmodium falciparum carbohydrate metabolism: a connection between host cell and parasite. 225 22

Among the various parameters that are supposed to play a role in aging at the cellular level, the "free radical theory" involves biochemical modifications that can be induced by radiation. Human embryonic lung fibroblasts were serially subcultivated at low density under chronic low dose rate irradiation (40 mrad/day) and in a normal environment. Irradiation increases cell attachment and the population doubling/day throughout their entire in vitro lifespan. Consequently, the doubling potential reached by irradiated cells was higher than that of control cultures. Finally, the total number of cells produced under chronic irradiation was 8-14 times higher than in a normal environment. These results are discussed with respect to the increased enzymatic activities (superoxidismutase, catalase, glutathion-reductase, G6PD) found in some irradiated organisms.
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PMID:Effects of a very low dose rate of chronic ionizing radiation on the division potential of human embryonic lung fibroblasts in vitro. 374 71

N-acetylcysteine (NAC) is often administered to respiratory patients with histories of exposure to noxious agents (e.g. cigarette smoke and atmospheric pollutants), which are known to act as glutathione (GSH) depletors and as cancer initiators and/or promoters. Since NAC is a precursor of intracellular GSH, we investigated its effects on GSH metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. In vitro, NAC induced a significant increase in oxidized glutathione (GSSG) reductase activity in rat liver preparations and counteracted the mutagenicity of direct-acting compounds (such as epichlorohydrin, hydrogen peroxide, 4-nitroquinoline-N-oxide and dichromate), as a result of its reducing and scavenging properties. At high concentrations, the drug completely inhibited the mutagenicity of procarcinogens (cigarette smoke condensate, tryptophan pyrolysate, cyclophosphamide, 2-aminofluorene, benzo(a)pyrene and aflatoxin B1) by binding their electrophilic metabolites. In contrast, their metabolic activation was stimulated by decreasing NAC concentrations, especially when liver preparations from enzyme-induced rats were used. Lung and liver subcellular preparations of rats treated in vivo with NAC, in various combinations with enzyme inducers and/or GSH depletors, also affected the mutagenicity of a number of compounds. NAC generally increased intracellular GSH and restored its levels following depletion. It did not affect the levels nor the spectral properties of cytochromes P-450 in pulmonary and hepatic microsomes, whereas it stimulated, especially in Aroclor-pretreated animals, cytosolic enzyme activities involved in NADP or GSSG reduction (G6PD, 6PGD and GSSG reductase) and in the reductive detoxification of xenobiotics (DT diaphorase). When administered with the diet, at a nontoxic posology (120 mg/kg b.w.), NAC markedly inhibited the induction of lung tumors in mice by a potent carcinogen (urethane).
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PMID:Metabolic, desmutagenic and anticarcinogenic effects of N-acetylcysteine. 380 42

The use of volatile butylnitrite in place of sodium nitrite for the in vitro production of methemoglobin was explored in studies of G6PD-deficient red cells and for measurements of the red cell methemoglobin reductase activity. It was found that butylnitrite vapor caused a more rapid oxidation of intracellular hemoglobin than sodium nitrite and required fewer washes for removal. Hence a more rapid preparation of the cells was possible. Both cytochemical detection of G6PD-deficient cells in a female heterozygote for G6PD deficiency and the screening test for a methemoglobin reductase deficiency could be performed with butylnitrite as well as with sodium nitrite. This small modification of these standard procedures promises to save time and facilitate processing of many samples during genetic screening of relevant populations.
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PMID:The laboratory use of butylnitrite for the production of methemoglobin. 403 56

The present studies were performed to evaluate the role of zinc in the regulation of testosterone 5 alpha-reduction by the 800 g supernatants prepared from human benign prostate hyperplasia specimens. The results show that when zinc is added at low concentrations the 5 alpha-reduction of testosterone is increased but at higher cation concentrations the metabolism is significantly inhibited. This decrease was mediated by both a non-competitive inhibition of the binding of testosterone to the 5 alpha-reductase enzyme and by a reduction in the formation of the NADPH cofactor. We have also demonstrated that the decreased synthesis of NADPH was produced by a competitive inhibition of both G6P and NADP binding to the G6PD enzyme. The data also suggests that the increase in testosterone metabolism observed at low zinc concentrations does not produce any changes in the binding of testosterone to the 5 alpha-reductase enzyme. In spite of the above observations we were unable to establish any correlation between the endogenous zinc content of the tissue and the in vitro capacity of the BPH samples to 5 alpha-reduce testosterone. The present study suggests a possible physiological role for the regulation of testosterone metabolism by zinc in the human prostate gland.
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PMID:The effect of zinc on the 5 alpha-reduction of testosterone by the hyperplastic human prostate gland. 620 Jul 3

In vitro studies on primaquine have been carried out to examine its ability to stimulate the oxidative pathway of glucose metabolism in human erythrocytes and in vivo studies were carried out after ingestion of the drug to determine plasma levels and to investigate the formation of metabolites and the effects of the drug on human erythrocytes. These investigations showed that:1) Two mechanisms are involved in the stimulation of the oxidative pathway. This was demonstrated by comparing the effects of methylene blue, ascorbic acid, primaquine, and other drugs on normal, glutathione-reductase-deficient, and G6PD-deficient erythrocytes. A start was made towards classifying drugs according to the mechanism by which they stimulate CO(2) production.2) Following oral ingestion of primaquine, three as yet unidentified metabolites were present, two in the plasma and one in the urine. The rapid disappearance of primaquine from the plasma (within 24 hours) was confirmed.3) Two factors that stimulate glucose oxidation in human erythrocytes were found in plasma; one occurred only in fresh plasma, when EDTA was present, and the other occurred in all plasma and serum samples studied.4) The erythrocytes of blood drawn 24 hours after the ingestion of primaquine (after primaquine had disappeared from the plasma) showed increased ability to oxidize glucose.It is not yet known whether serum or plasma prepared from blood drawn 24 hours after ingestion of primaquine has the ability to increase the oxidation of glucose.
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PMID:Toxicology of the 8-aminoquinolines and genetic factors associated with their toxicity in man. 697 50

Two new glucose-6-phosphate dehydrogenase (G6PD, D-glucose 6-phosphate: NADP oxido reductase, E.C. 1.1.1.49) variants, designated G6PD Napoli and G6PD Ferrara II, are described in propositi from two unrelated families. Characterization side by side of the two variants according to W.H.O. recommendations reveals minor differences which are mostly related to utilization of artificial substrates (increased in both cases as compared with normal G6PD type B). Other properties, which are not significantly distinctive between the two variants, are an enzyme activity amounting to nearly 20% of normal, a decreased electrophoretic mobility, decreased Km values for glucose-6-phosphate and NADP, normal thermostability and biphasic pH curves. However, marked differences emerged between the two variants and between either variant and G6PD B as well, when a number of microtechniques were used. These were: (1) the half-lives of G6PD Napoli and G6PD Ferrara II are 16 and 29 d, respectively, while that of G6PD B is 63 d; (2) the specific activities, measured by a method involving direct estimation of G6PD protein on sodium dodecyl sulphate polyacrylamide gel electrophoretic tracings, are 166 I.U./mg (G6PD Napoli) and 59 I.U./mg (G6PD Ferrara II), as compared with normal value of 180 I.U./mg (G6PD B). On the whole, these findings allow the conclusion that the deficiency of catalytic activity is related to an accelerated though distinctive decay of both mutant enzyme proteins within the affected erythrocytes and that a significant impairment of catalytic efficiency is also involved, as a result of the underlying structural mutation in the case of G6PD Ferrara II.
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PMID:G6PD Napoli and Ferrara II: two new glucose-6-phosphate dehydrogenase variants having similar characteristics but different intracellular lability and specific activity. 725 90

The relationship between D-glucose-6-phosphate: NADP oxido-reductase (E.C.1.1.1.49; glucose-6-phosphate dehydrogenase; G6PD) deficiency and homozygous sickle cell (SS) disease was examined in 120 patients. The proportions of hemizygotes (22.6%) was slightly more than that observed, and the combined proportions of heterozygotes and homozygotes (28.3%) were slightly less than would be expected, in the general population, but the differences were not significant. However, the proportion of patients of abnormal G6PD status in the 10-19 years age group was 41.7%, significantly more than that found in the 20-29 years age group (0.02 less than P less than 0.05), or expected in the general population (P=0.05). Possible reasons for this are discussed. Difference in G6PD status did not affect the total haemoglobin concentration, reticulocyte count, unconjugated serum bilirubin or Hb F concentration, irreversibly sickled cell counts or plasma haemoglobin concentration, and there was no demonstrable correlation between clinical severity or leg ulceration and abnormal G6PD status.
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PMID:Glucose-6-phosphate dehydrogenase deficiency and homozygous sickle cell disease in Jamaica. 737 31

Congenital hemolytic anemias resulting from PK, PFK, and G6PD enzyme deficiencies have been reported in domestic animals. Dogs with PFK deficiency may have episodes of intravascular hemolysis with hemoglobinuria in addition to a persistent compensated hemolytic anemia. Patients with mild G6PD deficiency are not anemic but may show increased susceptibility to oxidant-induced erythrocyte injury. Persistent methemoglobinemia has been reported in dogs and cats with methemoglobin reductase enzyme deficiency. Affected animals have cyanotic-appearing mucous membranes but show no or only mild clinical signs attributable to hypoxemia. Enzyme assays are usually done after acquired causes of hemolytic anemia and methemoglobinemia have been ruled out.
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PMID:Congenital erythrocyte enzyme deficiencies. 886 87

Congenital methemoglobinemia is a relatively rare clinical disorder characterized by life-long cyanosis, caused by either an inherited mutant hemoglobin (Hb-M) or deficiency of physiologically active NADH-dependent methemoglobin reductase (NADH-MR). NADH-MR deficiency leads to two different types of recessive congenital methemoglobinemia. In type I, cyanosis is the only major symptom and NADH-MR deficiency is restricted only to the red blood cells. In type II, cyanosis is associated with severe mental retardation and neurological impairment. The objective of this study is to establish the cause of cyanosis in our cases of congenital methaemoglobinemia. Erythrocyte NADH-MR activity was assayed spectrophotometrically. Spectral analysis of the hemolysate treated with potassium ferricyanide was recorded between 400-700 nm and Hb electrophoresis on starch gel at pH 7.0 was done to rule out the presence of Hb-M. NADH-MR deficiency was detected in 3 families. There was a history of consanguinity in one of these cases. The three propositi presented with breathlessness, fever and peripheral cyanosis. There was no history of cardiac illness or exposure to drugs and chemicals. There were no signs and symptoms of mental retardation. The presence of Hb-M was ruled out. Hb-A2, Hb-F, G6PD activity and reduced glutathione levels were normal. NADH-MR activity in all the cases ranged from 4.1 to 9.2 IU/g Hb (normal range 7.0-24.0 IU/g Hb). We describe NADH-MR deficiency in three unrelated cases (age 4 months to 6 years) where the activity of the enzyme was 30-40% of normal. These three cases of congenital methemoglobinemia are due to type-I NADH-MR deficiency without mental retardation.
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PMID:Congenital methemoglobinemia due to NADH-methemoglobin reductase deficiency in three Indian families. 1280 31


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