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

Unlike erythrocytes from elderly humans, red blood cells from old mice are not more sensitive than are cells from young animals to lysis in hypotonic solutions, probably because the mean corpuscular volume decreases rather than increases with age in this species. However, when subjected to an oxidant stress (sodium ascorbate) red blood cells from old animals accumulate more methemoglobin and fewer remain intact than is the case with red blood cells from young mice. The data suggest that this increased vulnerability to oxidative damage is manifest relatively early in the lifespan of red blood cells from old animals and is not solely a property of the older cells. The pathogenesis of the decreased resistance to peroxidation is not known, but it does not appear to be the result of changes in reduced glutathione, NADH: methemoglobin reductase, superoxide dismutase, glutathione reductase, glutamic-oxaloacetic transaminase, or glucose 6-phosphodehydrogenase.
 ...
PMID:Age-related increase in erythrocyte oxidant sensitivity. 717 1

A soluble erythrocyte cytochrome b5 was purified as the substrate of methemoglobin reductase and an electron carrier to methemoglobin. The isoelectric point of this protein was at pH 4.3, and E0' was -0.010 at pH 7.0.. The Km value of the enzyme for this protein was 1 x 10(-4) M, and the turnover number (k5) was 3.4 x 10(4) min-1, with NADH as an electron donor at pH 7.0. The optimum pH of the enzyme was pH 4.6 for ferricyanide and pH 5.5 for cytochrome b5, with a shoulder of activity at pH 7 to 9 for both substrates. The rate equation which represents the reduction of either methemoglobin or cytochrome c was obtained as a function of methemoglobin or cytochrome c, methemoglobin reductase, and cytochrome b5 by considering the E . S complex for both reductase and cytochrome b5, and the rate constants involved were determined. The rate constants between methemoglobin and reduced cytochrome b5 (k1, M-1 min-1) were 1.6 x 10(4), 3.1 x 10(6), and 4.1 x 10(6) at pH 7.0, pH 5.2, and pH 5.0, respectively. The rate constants between the reduced enzyme and oxidized cytochrome b5 (k'3, M-1 min-1) were 4.3 x 10(8), 12 x 10(8), and 9.3 x 10(8) at pH 7.0, pH 5.2, and pH 5.0, respectively. The rate constant between reduced hemoglobin and oxidized cytochrome b5 (k2) was 35 M-1 min-1 at pH 7.0. The theoretical Km for methemoglobin was 2.1 M at an infinite enzyme concentration at pH 7.0
 ...
PMID:Properties of methemoglobin reductase and kinetic study of methemoglobin reduction. 724 Jan 53

The changes in absorption spectra between 450 and 650 nm during the reduction of methemoglobin A, (alpha 2+ beta 3+)2, and (alpha 3+ beta 2+)2 valency hybrids by the system including ferredoxin and ferredoxin-NADP reductase were studied under anaerobic conditions. During the reduction of methemoglobin A, the isosbestic points gradually shifted to different positions. These shifts were clearly observed in the presence of inositol hexaphosphate, i.e. the isosbestic points were initially observed at 525 and 603 nm, and these shifted to 529 and 599 nm, respectively, suggesting that the intermediate hemoglobins are produced during the process of the reaction. This was confirmed by the isoelectric focusing electrophoresis of the partially reduced methemoglobin solutions with ferredoxin-NADP reductase system on Ampholine-polyacrylamide gel plate. On the other hand, the absorption spectra of alpha 2+ beta 3+)2 and (alpha 3+ beta 2+)2 changed with excellent isosbestic points during th reductive reaction by ferredoxin-NADP reductase system, i.e. (alpha 2+ beta 3+)2 at 526 and 601 nm and (alpha 3+ beta 2+)2 at 529 and 599 nm. From these results, the mechanism of methemoglobin reduction by ferredoxin-NADP reductase system was suggested. 1) There are two pathways for the reduction of methemoglobin including (formula, see text). 2) The beta chains of methemoglobin may be more susceptible to the reduction than the alpha chains in tetrameric methemoglobin, and thereby the (alpha 3+ beta 2+)2 valency hybrid accumulated at the halfway point of the reaction. 3) The shift in isosbestic points of methemoglobin reduction (525 nm leads to 529 nm, 603 nm leads to 599 nm) is due to the accumulation of (alpha 3+ beta 2+)2, whose isosbestic points during the reduction by the ferredoxin-NADP reductase systems were 529 and 599 nm.
 ...
PMID:Reduction of methemoglobin by ferredoxin and ferredoxin-NADP reductase system. 726 9

Native and modified methemoglobin (beta-93-SH groups blocked) were reduced by NADH-dependent methemoglobin reductase in the absence and the presence of organic phosphate (inositol hexaphosphate). These experiments were performed with dilute as well as concentrated methemoglobin solutions (physiological heme concentration). It is shown that: (a) in dilute solutions the blockage of beta-93-SH groups lowers the rate of methemoglobin reduction in the absence of organic phosphate but the rates of native and modified methemoglobin reduction are similar in the presence of organic phosphate; (b) at physiological heme concentration the blockage of beta-93-SH groups does not affect the rate of reduction but the organic phosphate stimulates the reduction of both native and modified methemoglobins in a similar fashion, as it does in dilute solutions. It is concluded that, although in dilute solutions the blockage of beta-93-SH groups alters the reduction rate, at physiological heme concentration the presence of free beta-93-SH groups does not have any significant effect on methemoglobin reduction. On the contrary, the organic phosphates do accelerate the rate of reduction at all ranges of heme concentration.
 ...
PMID:The influence of beta-93 sulfhydryl groups, organic phosphate and heme concentration on methemoglobin reduction. 729 82

Erythrocytes from heterozygous carriers of the high oxygen affinity mutant hemoglobin, Hb Wood, demonstrate lower rates of methemoglobin reduction than normal human red cells when incubated in the in vitro system of Beutler and Baluda. The rate of methemoglobin reduction in red cells from an individual who is heterozygous for both NADH-methoglobin reductase deficiency and Hb Wood shows the combined effects of the two mutations.
 ...
PMID:Methemoglobin reduction in red cells: effect of a high oxygen affinity hemoglobin. 735 Sep 31

The oxygen binding properties of Hb M Hyde Park (92 beta, histidine leads to tyrosine) were reinvestigated directing special care to testing the wave length-dependence of the oxygen equilibrium curve and to stabilizing hemoglobin samples using a methemoglobin reductase system. There was no indication that the Hb M Hyde Park fraction separated on a DEAE Sephadex column contained an unknown hemoglobin derivative which appeared in earlier studies. Contrary to earlier observations, there was no significant wave length-dependence of the equilibrium curve of Hb M Hyde Park, verifying the spectrophotometric determination of oxygen saturation. The reductase system satisfactorily reduced the normal alpha chain met hemes without reducing the abnormal beta chain met hemes. The oxygen binding property of Hb M Hyde Park is characterized by 3 to 4 times higher oxygen affinity than that for normal hemoglobin, complete loss of cooperativity, and substantially preserved Bohr effect. These results are consistent in part but not entirely with those observed by earlier investigators. The oxygen affinity of Hb M Hyde Park is between the affinity of the oxy structure and the deoxy structure of normal hemoglobin. Oxygen equilibrium curve of red cell suspension and whole hemolysate containing Hb M Hyde Park were biphasic, indicating that Hb M Hyde Park also exhibited the high oxygen affinity in those samples.
 ...
PMID:Further studies on the functional properties of hemoglobin M Hyde Park. 739 Aug 59

The reduction of methemoglobin by NADPH-flavin reductase of human erythrocytes through flavin was studied under various conditions using a reconstituted methemoglobin reductase system. The reduction of methemoglobin by the reconstituted enzyme system could be easily detected with flavin at the physiological concentration (e.g., 0.1-1.0 microM), and the rates obtained with 0.1 and 1.0 microM FMN were 0.19 and 2.2 nmol heme reduced per min per ml, respectively, in the absence of oxygen. FMN was more effective than FAD in reduction by the reconstituted enzyme system, and oxygen decreased the rate of the reduction. The reduction of methemoglobin by the reconstituted enzyme system with flavin at a physiological concentration proceeded as a zero order reaction. These results apparently suggest that the NADPH-flavin reductase system is able to reduce methemoglobin in erythrocytes at a moderate speed with about 1 microM flavin, and the reduction was estimated to vary from less than 1% to about 20% of that by the NADH-cytochrome b5 reductase system with 1 microM cytochrome b5, depending on the uptake of flavin by human erythrocytes.
 ...
PMID:Reduction of methemoglobin through flavin at the physiological concentration by NADPH-flavin reductase of human erythrocytes. 740 Jan 18

Methemoglobin reduction in human red cells involves successively an electron transport from NADH to a soluble form of cytochrome b5 (step 1) and from cytochrome b5 to methemoglobin (step 2). Step 1 is catalysed by an enzyme, soluble NADH:cytochrome b5 reductase (EC 1.6.2.2). Step 2 is non-enzymatic and involves complementary electrostatic interactions between acidic residues of cytochrome b5 and basic residues of hemoglobin [Gacon et al. (1980) Proc. Natl Acad. Sci. USA, 77, 1917-1921]. Here we present data indicating a similar mode of interactions occurring in step 1 between cytochrome b5 reductase and cytochrome b5. These results have been obtained by using the combined isoelectric focusing/electrophoresis method [Righetti et al. (1978) J. Chromatogr. 166, 455-460] allowing a direct titration of both entities either separately or in a mixture. This is the first report on the obtention of a direct titration curve of an enzyme visualized after specific staining (zymogram). The pH dependence of the Michaelis constant for cytochrome b5 is also in agreement with the hypothesis that electrostatic charges, which are maximal below pH 7.0, are essential in the interaction between cytochrome b5 and its reductase.
 ...
PMID:Direct enzyme titration curve of NADH: cytochrome b5 reductase by combined isoelectric focusing/electrophoresis. Interactions between enzyme and cytochrome b5. 744 61

In this study we present evidence that in human erythrocytes NADH-cytochrome b5 reductase (methemoglobin reductase) is not only soluble but also tightly bound to the membrane. The membrane methemoglobin reductase-like activity is unmasked by Triton X-100 treatment, and represents about half of the total activity in the erythrocytes. Like the amphiphilic microsomal-bound cytochrome b5 reductase, the erythrocyte membrane-bound enzyme is solubilized by cathepsin D. Because this treatment is effective on unsealed ghosts but not on resealed (inside-in) ghosts, it is concluded that the enzyme is strongly bound to the inner face of the membrane. The erythrocyte membrane enzyme is antigenically similar to the soluble enzyme. The two forms of enzyme are specified by the same gene, in that both were found defective in six patients with recessive congenital methemoglobinemia. We suggest that the cytochrome b5 reductase of the erythrocyte membrane is the primary gene product. A posttranslational partial proteolysis probably gives rise to the soluble form of the enzyme, which serves as a methemoglobin reductase.
 ...
PMID:Membrane-bound cytochrome b5 reductase (methemoglobin reductase) in human erythrocytes. Study in normal and methemoglobinemic subjects. 745 47

Treatment of rats with daily doses of 20 mg of lindane/kg for 3 consecutive days led to the accumulation of the insecticide in several tissues, including erythrocytes and liver. Lindane did not alter the hematocrit and hemoglobin concentration but reduced methemoglobin levels by 17%. Red blood cells from controls and lindane-treated rats, exposed to t-butyl hydroperoxide, exhibited comparable rates of oxygen uptake and visible chemiluminescence, whereas the induction period that precedes oxygen uptake was significantly enhanced in the latter group. Lindane treatment did not modify the activity of erythrocyte glutathione peroxidase, glucose-6-phosphate dehydrogenase, catalase, and methemoglobin reductase, being the total content of glutathione and superoxide dismutase activity significantly increased. The liver from lindane-treated rats showed an enhanced microsomal pro-oxidant activity, evidenced by higher cytochrome P450 content and NADPH-cytochrome c reductase and NADPH oxidase activities. The higher enzyme activities led to an increased superoxide anion generation (adrenochrome formation) and lipid peroxidation (measured either by the production of thiobarbituric acid reactants and spontaneous visible chemiluminescence). Concomitantly, liver glutathione content and the activity of glutathione peroxidase-glutathione reductase couple were augmented by lindane treatment, without any change in superoxide dismutase activity, together with a reduction in that of catalase. Results suggest that lindane does not alter the prooxidant/antioxidant status of the erythrocyte in conditions of a significant cellular accumulation of the insecticide, which might exert direct action on enzymatic systems leading to enhanced superoxide dismutase activity and glutathione content.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Acute lindane intoxication: a study on lindane tissue concentration and oxidative stress-related parameters in liver and erythrocytes. 751 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>