Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a single interaperitoneal injection (6 mg/kg body weight) of aflatoxin B1 in propylene glycol on pyridine nucleotides and NDP linked dehydrogenases was studied 24 h after administration of the toxin. The liver showed a decrease in total proteins and pyridine nucleotides though levels of NADP and NADPH remained unchanged. Levels of NAD and NADH were decreased. The activities of hepatic of hwpRIX of hepatic malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were not altered though ICDH showed an increase when expressed on protein basis. However, there was a significance decrease in the activity of combined HMP dehydrogenases. Adipose tissue showed increased activities of the HMP dehydrogenasess.
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PMID:Effect of aflatoxin B1 on pyridine nucleotides and NADP linked dehydrogenases. 0 75

Transformation frequencies of 4 x 10(-5) were obtained in chromosome-mediated gene transfer experiments using human cell line HeLa S3 as donor and mouse cell line A9 as recipient. This high frequency of interspecific transformation was achieved by treating the recipient cells with dimethylsulfoxide in addition to other facilitators. The high frequency of transformation correlated positively with transgenome size on the basis of both co-transfer of linked markers and chromosome analysis. The syntenic human markers glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP(+) 1-oxidoreductase, EC 1.1.1.49) and phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3) were sometimes transferred together with the selected X-linked prototrophic marker hypoxanthine phosphoribosyltransferase (IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) into murine somatic cells. Donor human chromosome material could be demonstrated cytologically in some of the transformed cell lines. Transformants exhibited various rates of loss of the human hypoxanthine phosphoribosyltransferase marker when grown under nonselective conditions. These results reveal a broader range of possible interspecific transgenome sizes than has been recognized in the past. The largest transgenomes consist of cytologically detectable donor fragments and contain syntenic markers that are not closely linked to the selected marker.
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PMID:Co-transfer of human X-linked markers into murine somatic cells via isolated metaphase chromosomes. 27 34

The NADPH oxidase of phagocytic cells is important for the efficient killing and digestion of ingested microbes. A very unusual low-potential cytochrome b (b-245) is the only redox molecule to have been identified in this system. The FAD-containing flavoprotein that binds NADPH and transfers electrons to the cytochrome has eluded identification for three decades. We show here that the haem/FAD ratio in the membranes does not change significantly on activation of this oxidase, indicating that the FAD is present in the membranes from the outset and not recruited from the cytosol. The FAD content of membranes from cells of patients with X-linked chronic granulomatous disease (CGD) lacking the cytochrome b was roughly one-quarter of that in normal subjects and in autosomal recessive CGD patients lacking the cytosolic protein p47-phox. Similar low amounts of FAD were present in uninduced promyelocytic (HL60) cells, suggesting that the low amount of FAD in cells from X-CGD patients was probably unrelated to this oxidase system. Cytochrome b-245 appears to bind both the haem and FAD, in a molar ratio of 2:1. The e.p.r. signal of the purified cytochrome was weak and had an asymmetric g(z) peak at g = 3.31. The purified cytochrome could be partially reflavinated (about 20%) in the presence of lipid. Amino acid sequence homology was detected between the beta-subunit of this cytochrome b and the ferredoxin-NADP+ reductase (FNR) family of reductases in the putative NADPH- and FAD-binding sites. 32P-labelled 2-azido-NADP was used as a photoaffinity label for the NADPH-binding site. Labelling that was competed off with NADP was observed in the region of the beta-subunit of the cytochrome. No labelling was seen in this region in X-CGD in three subjects in whom this cytochrome was missing and in a third in whom it was present but bore a Pro-His transposition in the putative NADPH-binding site. These studies indicate that cytochrome b-245 is a flavocytochrome, the first described in higher eukaryotic cells, bearing the complete electron-transporting apparatus of the NADPH oxidase.
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PMID:Cytochrome b-245 is a flavocytochrome containing FAD and the NADPH-binding site of the microbicidal oxidase of phagocytes. 132 Mar 78

We describe a new glucose-6-phosphate dehydrogenase mutant, G-6-PD Titusville. The propositus is a 7-month-old black male infant with a transient hemolytic episode. The mutant enzyme is characterized by abnormal electrophoretic mobility, thermolability, Km for NADP, abnormal deamino NADP use and a decreased sensitivity to inhibition by NADPH. G-6-PD activity of hemolysate, as measured under optimal in vitro conditions, was not initially decreased, whereas fibroblasts, granulocytes, and platelets showed a markedly decreased level of enzyme activity. These properties identify G6PD Titusville as a unique variant of this X-linked, housekeeping enzyme. We conclude that although the propositus with G6PD Titusville had a transient hemolytic episode, we cannot be certain whether this association was a causative one.
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PMID:Characterization of a new G6PD variant: G6PD Titusville. 291 31

A mouse with X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency has been recovered in offspring of 1-ethyl-1-nitrosourea-treated male mice. The activity alteration was detected in blood but can also be observed in other tissue extracts. Hemizygous, heterozygous, and homozygous mutants have, respectively, about 15, 60, and 15% G6PD remaining activity in the blood as compared to the wild type. Erythrocyte indices did not show differences between mutants and wild types. The mutation does not affect the electrophoretic migration, the isoelectric point, or the thermal stability. Kinetic properties, such as the Km for glucose-6-phosphate or for NADP and the relative utilization of substrate analogues, showed no differences between wild types and mutants with the exception of the relative utilization of deamino-NADP which was significantly lower in mutants. This is presently the only animal model for X-linked G6PD deficiency in humans.
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PMID:X-linked glucose-6-phosphate dehydrogenase deficiency in Mus musculus. 337 61

Mouse A9 cells, L-cell-derived mutants deficient in hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) were found to be incapable of binding (125)I-labeled epidermal growth factor (EGF) to the cell surface. The A9 cells were fused with human diploid fibroblasts (WI-38) possessing EGF-binding ability, and human-mouse cell hybrids (TA series) were isolated after hypoxanthine/aminopterin/thymidine/ouabain selection. Analyses of isozyme markers and chromosomes of four representative clones of TA hybrids indicated that the expression of EGF-binding ability is correlated with the presence of human chromosome 7 or 19. Four subclones were isolated from an EGF-binding-positive line, TA-4, and segregation of EGF-binding was found to be concordant with the expression of human mitochondrial malate dehydrogenase (MDHM; L-malate:NAD(+) oxidoreductase, EC 1.1.1.37), a marker for chromosome 7, but not with glucosephosphate isomerase (GPI; D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9), a marker for chromosome 19. Furthermore, evidence from 27 clones of AUG hybrids that were produced between A9 and another human fibroblast line, GM1696, carrying an X/7 chromosome translocation indicated that EGF-binding ability segregates together with human MDHM and two X-linked markers, HPRT and glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate:NADP(+) 1-oxidoreductase, EC 1.1.1.49), that are located on the translocation chromosome 7p(+). These results permit assignment of the gene, designated EGFS, which is associated with the expression of EGF-binding ability, to human chromosome 7 and its localization to the p22-qter region. Because the EGF receptor is reported to be a glycoprotein the EGFS could be either a structural gene(s) for receptor protein or a gene(s) for modifying the receptor protein through glycosylation.
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PMID:Genetics of cell surface receptors for bioactive polypeptides: binding of epidermal growth factor is associated with the presence of human chromosome 7 in human-mouse cell hybrids. 696 72

FX is a red cell NADP(H)-binding protein that has been well defined biochemically and immunologically but whose function is still unknown. Preliminary data indicated that the levels of this protein are significantly increased in hemizygotes, heterozygotes, and homozygotes for the G6PD Mediterranean mutant, thus raising the question of whether or not the individual variation in FX levels is more or less directly influenced by X-linked genes. The present study, based on a large series of population and family data collected in Sardinia, confirms unequivocally the above mentioned interaction, but shows at the same time that the variances in FX levels "between sibships" are 2-3 times larger than those "within sibships," when the analysis is done separately for the G6PD-normal or the G6PD-deficient sibs. From the comparison of the interclass and intraclass correlation coefficients, it appears that about 60% of the total variation of FX is of genetic origin. Moreover, the FX levels of children, analyzed in a pairwise manner, were found to be more positively correlated with those of their fathers (r = 0.39) than with those of their maternal grandfathers (0.20). This latter finding obviously favors the conclusion that "autosomal" rather than "X-linked" genes are involved in the determination of the FX levels.
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PMID:Genetic variation in the quantitative levels of an NADP (H)-binding protein (FX) in human erythrocytes. 744 21

Defects in gp91-phox, the large subunit of cytochrome b558 (b-245) give rise to X-linked chronic granulomatous disease (CGD), a rare inherited condition characterized by an extreme susceptibility to bacterial and fungal infection. In the majority of cases, the phagocytes are unable to generate any superoxide owing to complete absence of the flavocytochrome. However, a small minority of these patients do have some phagocytic oxidase activity. We describe here an analysis of the molecular basis of the disease in three such variant patients with lesions in the gene coding for gp91-phox on the X chromosome. Three different genetic lesions were found, resulting in the substitution of tyrosine for cysteine 244, a deletion of one of three lysines 313 through 315, and the deletion of the six C-terminal amino acids, respectively. The functional consequences of these defects on oxidase activity was a reduction to 12%, 3.6%, and 2.1% of the normal levels, respectively. Corresponding levels of gp91-phox were 20%, 8%, and 16% of normal classifying these patients as X91-. Microbicidal assays showed that killing of Staphylococcus aureus was grossly impaired in cells in which there was 12% normal activity. This implies that if gene therapy is to be applied, it must restore oxidase activity to a much higher level than that present in the cells of this patient. The sites of two of the mutations were analyzed on a model of the C-terminal half of the gp91-phox, based on the crystal structure of the homologous protein ferrodoxin NADP reductase. Possible structural consequences of the mutations were examined.
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PMID:Molecular analysis in three cases of X91- variant chronic granulomatous disease. 757 66

Human glucose-6-phosphate dehydrogenase (G6PD) deficiency almost invariably results from the presence of missense mutations in the X-linked gene encoding G6PD. The common African deficient variant G6PD A- differs from the normal G6PD B by two amino acid substitutions. Only one of these mutations is found on its own, resulting in the nondeficient variant G6PD A. Deficiency is always associated with decreased G6PD activity in red cells, leading to a variety of clinical manifestations. A group of deficient variants, including A-, have near-normal affinity for the substrates G6P and NADP. In these cases, deficiency is caused by a decreased number of catalytically active molecules per cell due to intracellular instability of the mutated G6PD, although the mechanism for this in vivo instability is unknown. Here we report that in vitro folding of the A- variant mainly renders partially folded polypeptides that do not undergo the dimerization required for activity. Under the same conditions, the nondeficient variants B and A undergo folding to produce active dimers with normal mobilities in native gels and normal kinetic properties. The loss of intrinsic folding determinants in the A- variant may underlie the mechanism of its in vivo instability.
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PMID:Unproductive folding of the human G6PD-deficient variant A-. 856 36

Two divergently oriented operons, strXU and strVW, located within the gene cluster for 5'-hydroxystreptomycin (5'-OH-Sm) biosynthesis in Streptomyces glaucescens strain GAL.0 (ETH 22794), were analysed by DNA sequencing and transcription/regulation studies. Three genes, strU and strVW, are conserved in a similar arrangement but in a different location within the str/sts gene cluster of the Sm-producing strain S. griseus N2-3-11. The four putative products resemble NDP-4-ketohexose 3,5-epimerases (StrX, M(r) 20.2 kDa), NAD(P)-dependent oxidoreductases (StrU, 45.6 kDa), and ABC-transporters (StrV, 61.8 kDa; StrW, 63.4 kDa). These genes are apparently involved in the biosynthesis of 5'-OH-Sm because the promoters of both operons are activated in trans by the activator StrR of S. griseus N2-3-11, when cloned in S. lividans 66 TK23. A sequence motif resembling the consensus sequence GTTCGActG(N)11CagTcGAAc for binding of StrR was identified within the intergenic region of strX and strV. Specific binding of StrR to this site was demonstrated by gel retardation assays using purified His*Tag-StrR.
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PMID:The str gene cluster for the biosynthesis of 5'-hydroxystreptomycin in Streptomyces glaucescens GLA.0 (ETH 22794): new operons and evidence for pathway-specific regulation by StrR. 862 39


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