UNIPROT:Q8NEX9 - FACTA Search

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Query: UNIPROT:Q8NEX9 (reductase)
26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is a membrane-bound glycoprotein localized in the endoplasmic reticulum. This enzyme has a key role in regulating local tissue glucocorticoid concentration, acting in vivo predominantly as an oxidoreductase. Previous attempts to purify the native enzyme have yielded a protein without reductase activity. To facilitate detailed studies on its structure and regulation, we have developed a method to purify the full-length human and rat 11beta-HSD1 with retention of their natural oxidoreductase activities. This procedure involved recombinant expression of these histidine-tagged enzymes in the yeast Pichia pastoris; large-scale culturing in a fermentor; and single-step purification by metal affinity chromatography. Both enzymes were 90-95% pure and exhibited dehydrogenase and reductase activities with K(M) values in agreement with those reported in the literature.
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PMID:Purification of full-length recombinant human and rat type 1 11beta-hydroxysteroid dehydrogenases with retained oxidoreductase activities. 1246 Jul 58

Using the unique preparation and detection techniques we devised for application of proteins to soft ionization mass spectrometry, we found many variant and abnormally modified proteins. Up to end of 2002, we have diagnosed 96 cases of variant hemoglobins(Hb), which include 45 different and 3 new species. We have diagnosed or confirmed the molecular weight difference of 64 cases of variant transthyretins (TTR), which include 14 different and 3 new species. We found the first 2 cases showing homozygote of TTR 119Thr-->Met, a high frequent non-amyloid variant among some European ethnicities. Variants of Cu, Zn-superoxide dismutase, 5 cases, 5 different species, were analyzed and the differences of molecular weight suggested by DNA analyses were confirmed. These are listed in the text. Cysteine 10 in TTR is modified in vivo and in vitro. We found a marked increase in s-sulfonated TTR in 4 patients with molybdenum cofactor deficiency and homocysteine conjugated TTR in 2 patients with methylene H4 folate reductase deficiency. The carbohydrate deficient transferrin was detected in 3 cases of carbohydrate deficient glycoprotein syndrome. The detection of these modified structures might be expected to be a new diagnostic index for these diseases, which are easily misdiagnosed. The improved reference method for HbA1C measurement was established using isotope(deuterium) labeled glycated and non-glycated hexapeptides from amino terminal of Hb beta-chain. We checked the discrepancies of HbA1c values by the routine method and the reference method we established. Most samples containing variant Hbs did not show correct HbA1c values by HPLC and some did not show correct values by immunoassay. We showed a typical example of an enormous increase in the glycation degree because of the amino acid substitution, which was shown clearly by electrospray ionization/mass spectrometry. (Nine figures and 4 tables were selected from 45 slides presented in the lecture.)
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PMID:[Detection and identification of variant and abnormally modified proteins by soft ionization mass spectrometry, unrivaled technique for clinical diagnosis]. 1265 89

At least three structural proteins in Paramecium bursaria Chlorella virus (PBCV-1) are glycosylated, including the major capsid protein Vp54. However, unlike other glycoprotein-containing viruses that use host-encoded enzymes in the endoplasmic reticulum-Golgi to glycosylate their proteins, PBCV-1 encodes at least many, if not all, of the glycosyltransferases used to glycosylate its structural proteins. As described here, PBCV-1 also encodes two open reading frames that resemble bacterial and mammalian enzymes involved in de novo GDP-L-fucose biosynthesis. This pathway, starting from GDP-D-mannose, consists of two sequential steps catalyzed by GDP-D-mannose 4,6 dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose epimerase/reductase, respectively. The two PBCV-1-encoded genes were expressed in Escherichia coli, and the recombinant proteins had the predicted enzyme activity. However, in addition to the dehydratase activity, PBCV-1 GMD also had a reductase activity, producing GDP-D-rhamnose. In vivo studies established that PBCV-1 GMD and GDP-4-keto-6-deoxy-D-mannose epimerase/reductase are expressed after virus infection and that both GDP-L-fucose and GDP-D-rhamnose are produced in virus-infected cells. Thus, PBCV-1 is the first virus known to encode enzymes involved in nucleotide sugar metabolism. Because fucose and rhamnose are components of the glycans attached to Vp54, the pathway could circumvent a limited supply of GDP sugars by the algal host.
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PMID:Paramecium bursaria Chlorella virus 1 encodes two enzymes involved in the biosynthesis of GDP-L-fucose and GDP-D-rhamnose. 1267 42

The ability of the testis to convert irreversibly androgens into estrogens is related to the presence of a microsomal enzymatic complex named aromatase, which is composed of a specific glycoprotein, the cytochrome P450 aromatase (P450arom) and an ubiquitous reductase. The aromatase gene is unique in humans and contained 18 exons, 9 of them being translated. In the rat testis we have immunolocalized the P450arom not only in Leydig cells but also in germ cells and especially in elongated spermatids. Related to the stage of germ cell maturation, we have shown that the level of P450arom mRNA transcripts decreases, it is much more abundant in pachytene spermatocytes and round spermatids than in mature germ cells whereas the aromatase activity is 2-4 fold greater in spermatozoa when compared to the younger germ cells. Using a highly specific quantitative competitive RT-PCR method we have evidenced that several factors direct the expression of the aromatase gene in Leydig cells, Sertoli cells, pachytene spermatocytes and round spermatids, and it is obvious that promoter PII is the main one but other promoters could be concerned. In the bank-vole testis we have observed a positive correlation between a fully developed spermatogenesis and a strong immunoreactivity for both P450arom and estrogen receptor beta not only in Sertoli cells but also in pachytene spermatocytes and round spermatids. Our recent data obtained from ejaculated human spermatozoa demonstrate the presence of aromatase both in terms of mRNA and protein, and in addition, we suggest that aromatase could be involved in the acquisition of sperm motility. Indeed in men the congenital aromatase deficiency is associated with severe bone maturation problems and sterility. Together with the widespread distribution of estrogen receptors in testicular cells these data clearly show that estrogens play a physiological role in the regulation of spermatogenesis in mammals.
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PMID:Aromatase expression and role of estrogens in male gonad : a review. 1274 6

Current strategies for both the primary and secondary prevention of coronary heart disease (CHD) focus on the traditional risk factors, such as hypertension, smoking cessation, and cholesterol, as the primary determinants of the cardiac risk profile, with particular emphasis on the reduction of low-density lipoprotein cholesterol (LDL-C) to targeted goal levels as endorsed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Large primary and secondary prevention trials with the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated varying reductions in cardiovascular events associated with similar changes in LDL-C levels, suggesting statins may possess additional beneficial effects on other risk factors. Retrospective analyses of many statin trials have evaluated the association between several polymorphic candidate genes (apolipoprotein E, stromelysin-1, beta-fibrinogen, cholesteryl ester transfer protein, lipoprotein lipase, hepatic lipase, and platelet glycoprotein III) which have been identified as predictors of disease severity and both metabolic and clinical response to statin therapy. These results suggest that statin therapy improves plasma lipid profiles in all patients, but preferentially benefits individuals who carry a high risk, variant genotype for these risk factors as compared to individuals with the wild-type genotype. These observations suggest that determining individual patient genotype may be useful in optimizing the benefits of statin therapy. These hypothesis-generating data need to be prospectively evaluated in genotyped patients.
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PMID:Genetic polymorphisms in emerging cardiovascular risk factors and response to statin therapy. 1284 89

Endothelium activation seems to represent one of the pathogenic mechanisms that induce the trombophilic state of the anti-phospholipid syndrome. The rationale behind such a statement lies on the demonstration that: (a) the major antigen of the anti-phospholipid antibodies (beta 2 glycoprotein I) can be expressed on the endothelial cell membrane, (b) the endothelial beta 2 glycoprotein I offers suitable epitopes for circulating antibodies, (c) the binding of anti-beta 2 glycoprotein I antibodies is capable to induce the appearance of a pro-coagulant and pro-inflammatory phenotype. Both in vitro and in vivo experimental models support such a hypothesis. Although a classical vasculitic process cannot be found in the anti-phospholipid syndrome there is indirect evidence that endothelial activation/damage does occur also in vivo. The demonstration that hydroxymethylglutaryl Co-enzyme A reductase enzyme inhibitors (statins) can block endothelial cell activation induced by anti-beta 2 glycoprotein I antibodies as well as by pro-inflammatory cytokines offers new therapeutical approaches.
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PMID:Endothelium as a target for anti-phospholipid antibodies and for therapeutical intervention. 1284 59

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.
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PMID:The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion. 1504 38

Concanavalin A (ConA) kills the procyclic (insect) form of Trypanosoma brucei by binding to its major surface glycoprotein, procyclin. We previously isolated a mutant cell line, ConA 1-1, that is less agglutinated and more resistant to ConA killing than are wild-type (WT) cells. Subsequently we found that the ConA resistance phenotype in this mutant is due to the fact that the procyclin either has no N-glycan or has an N-glycan with an altered structure. Here we demonstrate that the alteration in procyclin N-glycosylation correlates with two defects in the N-linked oligosaccharide biosynthetic pathway. First, ConA 1-1 has a defect in activity of polyprenol reductase, an enzyme involved in synthesis of dolichol. Metabolic incorporation of [3H]mevalonate showed that ConA 1-1 synthesizes equal amounts of dolichol and polyprenol, whereas WT cells make predominantly dolichol. Second, we found that ConA 1-1 synthesizes and accumulates an oligosaccharide lipid (OSL) precursor that is smaller in size than that from WT cells. The glycan of OSL in WT cells is apparently Man9GlcNAc2, whereas that from ConA 1-1 is Man7GlcNAc2. The smaller OSL glycan in the ConA 1-1 explains how some procyclin polypeptides bear a Man4GlcNAc2 modified with a terminal N-acetyllactosamine group, which is poorly recognized by ConA.
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PMID:Defects in the N-linked oligosaccharide biosynthetic pathway in a Trypanosoma brucei glycosylation mutant. 1507 56

alpha1-Microglobulin (alpha1m) is a 26-kDa plasma and tissue glycoprotein. The protein has a heterogeneous yellow-brown chromophore consisting of small unidentified prosthetic groups localized to a free thiol group (C34) and three lysyl residues (K92, K118, and K130) around the entrance to a hydrophobic pocket. It was recently reported that alpha1m can bind heme and that a C-terminally processed form of alpha1m degrades heme. It is shown here that alpha1m has catalytic reductase and NADH-dehydrogenase-like activities. Cytochrome c, nitroblue tetrazolium (NBT), methemoglobin, and ferricyanide were reduced by alpha1m. Comparison of the reduction rates suggests that methemoglobin is a better substrate than cytochrome c, NBT, and ferricyanide. The reactions with cytochrome c and NBT were mediated by superoxide anions since they were inhibited by superoxide dismutase. The addition of the biological electron donors NADH, NADPH, or ascorbate enhanced the reduction rate of cytochrome c approximately 30-fold. Recombinant alpha1m, which has much less chromophore than plasma and urine alpha1m, was a stronger reductant than the latter alpha1m forms. Site-directed mutagenesis of C34, K92, K118, and K130 and thiol group chemistry showed that the C34 thiol group was involved in the redox reaction but relies upon cooperation with the lysyl residues. The redox properties of alpha1m may provide a physiological protection mechanism against extracellularly exposed heme groups and other oxidants.
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PMID:Redox properties of the lipocalin alpha1-microglobulin: reduction of cytochrome c, hemoglobin, and free iron. 1568 11

This study was carried out to investigate the modulation of detoxicant enzyme activity and plasma lipidemic levels by 150 kDa glycoprotein isolated from Solanum nigrum Linne (SNL), which has been used as a hepatoprotective and anticancer agent in folk medicine. Our results in this study showed that SNL glycoprotein has a band with 150 kDa on the 10% sodium dodecyl sulfate polyacrylamide gel, and that it has a strong scavenging activity against lipid peroxyl radicals. We also evaluated the lipidemic levels of SNL glycoprotein, based on lipoproteins and activities of detoxicant enzymes in treatment with Triton WR-1339 or corn oil in vivo. When mice were treated with either Triton WR-1339 or corn oil in the absence of SNL glycoprotein, the number of plasma lipoproteins [triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL)] increased. However, when the mice were treated with either Triton WR-1339 or corn oil in the presence of SNL glycoprotein, the plasma lipoprotein levels (TG, TC and LDL) were significantly reduced. Similar results of SNL glycoprotein treatment were also produced in the activities of detoxicant enzymes. Namely, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were remarkably increased after treatment with SNL glycoprotein. In addition, the activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was reduced by SNL glycoprotein in cholestyramine-treated mice. For example, we found that it inhibits the activity of cholestyramine-induced hepatic HMG-CoA reductase at 40 microg head body weight g(-1) SNL glycoprotein. Collectively, these results pointed out that SNL glycoprotein can enhance the activities of detoxicant enzymes and bring about the inhibition of HMG-CoA reductase activity in vivo. Therefore, we speculate that SNL glycoprotein can be used as a cholesterol-lowering agent even at low concentrations.
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PMID:150 kDa glycoprotein isolated from Solanum nigrum Linne enhances activities of detoxicant enzymes and lowers plasmic cholesterol in mouse. 1574 54

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