Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.1.4 (xanthine dehydrogenase)
 1,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurospora crassa can utilize various purine bases such as xanthine or uric acid and their catabolic products as a nitrogen source. Four classes of mutants which affect the purine degradative pathway were isolated and studied. Mutants of the aln-1 class specifically lack allantoinase, while alc-1 mutants lack allantoicase. Mutants designated as xdh-1 cannot utilize hypoxanthine as a nitrogen source and are presumed to be deficient in xanthine dehydrogenase activity. A regulatory mutant, amr, was found to have only very low, uninduced levels of uricase, allantoinase, and allantoicase. None of these genes are closely linked to each other. The three initial enzymes involved in the catabolism of uric acid are controlled in a complex manner by both induction and repression. Several lines of evidence indicate that the true inducer of uricase and allantoicase is uric acid. The use of the newly isolated mutant strains made it possible to demonstrate that neither allantoin nor allantoic acid could act as inducers. Furthermore, hypoxanthine itself was shown to be ineffective as an inducer although it can be metabolized to form an inducer. A non-metabolizable analogue of uric acid, 8-azaxanthine, is a gratuitous inducer of these enzymes. Uricase and allantoicase were found to be synthesized coordinately, but they were not coordinately regulated with allantoinase. Both uricase and allantoicase are stable enzymes and do not undergo turnover; nor are they subject to feedback inhibition by ammonia. Allantoinase, however, is quite labile both in vivo and in vitro. This enzyme was found to turnover in vivo in the presence of cycloheximide with a half-life of approximately 20 minutes. The amr (for ammonia regulation) mutant cannot utilize a wide range of compounds, including purines, nitrate, and many amino acids as a nitrogen source and also displays a multiple enzyme loss. The amr gene appears to play a major role in the control of nitrogen metabolism. It is postulated that the amr locus encodes a regulatory protein which is required to activate transcription of the structural genes for a group of related enzymes involved in nitrogen metabolism.
 ...
PMID:Genetic and metabolic control of the purine catabolic enzymes of Neurospora crasse. 12 63

The characterization of mutants that are resistant to the herbicide chlorate has greatly increased our understanding of the structure and function of the genes required for the assimilation of nitrate. Hundreds of chlorate-resistant mutants have been identified in plants, and almost all have been found to be defective in nitrate reduction due to mutations in either nitrate reductase (NR) structural genes or genes required for the synthesis of the NR cofactor molybdenum-pterin (MoCo). The cholorate-resistant mutant of Arabidopsis thaliana, chl2, is also impaired in nitrate reduction, but the defect responsible for this phenotype has yet to be explained. chl2 plants have low levels of NR activity, yet the map position of the chl2 mutation is clearly distinct from that of the two NR structural genes that have been identified in Arabidopsis. In addition, chl2 plants are not thought to be defective in MoCo, as they have near wild-type levels of xanthine dehydrogenase activity, which has been used as a measure of MoCo in other organisms. These results suggest that chl2 may be a NR regulatory mutant. We have examined chl2 plants and have found that they have as much NR (NIA2) mRNA as wild type a variable but often reduced level of NR protein, and one-eighth the NR activity of wild-type plants. It is difficult to explain these results by a simple regulatory model; therefore, we reexamined the MoCo levels in chl2 plants using a sensitive, specific assay for MoCo: complementation of Neurospora MoCo mutant extracts.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Identification of two tungstate-sensitive molybdenum cofactor mutants, chl2 and chl7, of Arabidopsis thaliana. 153 67

Two nitrate reductase (NaR)-deficient mutants of pea (Pisum sativum L.), E1 and A300, both disturbed in the molybdenum cofactor function and isolated, respectively, from cv Rondo and cv Juneau, were tested for allelism and were compared in biochemical and growth characteristics. The F1 plants of the cross E1 X A300 possessed NaR and xanthine dehydrogenase (XDH) activities comparable to those of the wild types, indicating that these mutants belong to different complementation groups, representing two different loci. Therefore, mutant E1 represents, besides mutant A300 and the allelic mutants A317 and A334, a third locus governing NaR and is assigned the gene destignation nar 3. In comparison with the wild types, cytochrome c reductase activity was increased in both mutants. The mutants had different cytochrome c reductase distribution patterns, indicating that mutant A300 could be disturbed in the ability to dimerize NaR apoprotein monomers, and mutant E1 in the catalytic function of the molybdenum cofactor. In growth characteristics studied, A300 did not differ from the wild types, whereas fully grown leaves of mutant E1 became necrotic in soil and in liquid media containing nitrate.
 ...
PMID:Biochemical and genetic comparison of two nitrate reductase-deficient pea mutants disturbed in the cofactor. 347 18

In vitro assembly or complementation of a hybrid assimilatory nitrate reductase was attained by mixing a preparation of nitrate-induced N. crassa mutant nit-1 specifically with acid-treated (pH 2.5) bovine milk or intestinal xanthine oxidase, rabbit liver aldehyde oxidase, or chicken liver xanthine dehydrogenase. The complementation reaction specifically required induced nit-1, the only nitrate reductase mutant of Neurospora that lacked xanthine dehydrogenase and was unable to use hypoxathine or nitrate as a sole nitrogen source. The complementing activities of the above acid-treated enzymes correspond to their xanthine or aldehyde oxidizing activity profiles on sucrose density gradients. The resulting soluble, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductases are the same as the Neurospora wild type enzyme in sucrose density gradient profile, molecular weight, substrate affinities, and sensitivity to inhibitors and temperature. By analogy to a similar in vitro complementation of nitrate reductase in mixtures of induced nit-1 and individual nonalleic Neurospora mutants, or uninduced wild type, the complemented nitrate apparently consists of an inducible protein subunit (possessing inducible NADPH-cytochrome c reductase) furnished by nit-1 and a subunit from the acid-treated xanthine or aldehyde oxidizing system which can substitute for the constitutive component furnished by the other mutants or uninduced wild type. The data suggest that Neurospora nitrate reductase and the xanthine oxidizing system and aldehyde oxidase of animals, all of which are molybdenum-containing enzymes catalyzing the reduction of nitrate to nitrite, share a highly similar protein subunit.
 ...
PMID:In vitro assembly of Neurospora assimilatory nitrate reductase from protein subunits of a Neurospora mutant and the xanthine oxidizing or aldehyde oxidase systems of higher animals. 439 66

Mutants of Aspergillus nidulans resistant to methylammonium toxicity are simultaneously derepressed in the presence of ammonium for apparently all ammonium-repressible activities. Enzyme assays directly demonstrate derepression of nitrate, nitrite, and hydroxylamine reductases, xanthine dehydrogenase, urate oxidase, and allantoinase, whereas in vivo tests show that ammonium and methylammonium repression or inhibition (or both) is relieved in these mutants in pathways of nitrate assimilation, purine transport and degradation, and amino acid, amine, and amide catabolism. Ammonium and methylammonium uptake is apparently not defective in these mutants, for they grow normally on limiting levels of these ions as sole nitrogen source. There is no evidence that more than one gene can mutate to produce the methylammonium resistance (mea(R)) phenotype. Such mutations are semidominant in both heterocaryons and diploids. The ability of mea(R) mutations to effect derepression of activities specified by genes within another nucleus in a heterocaryon shows that the action of the mea product is not restricted to the nucleus. Three types of hypotheses might explain this generalized derepression. First, ammonium and methylammonium might not themselves be co-repressors but might require a metabolic conversion, blocked in these mutants, to become co-repressors. Secondly, the mea locus might specify an activity expressed in mea(R) but not wild-type (mea(S)) strains, which diminishes the concentration of ammonium and methylammonium participating in co-repression. Finally, ammonium repression might involve a macromolecular control element specified by the mea(R) locus and common to many or all ammonium-repressible systems. The existence of "regulation reversal mutations" at the mea(R) locus and the lack of uniformity and coordination with which different enzymatic activities respond to mutational derepression is most compatible with the last type of hypothesis.
 ...
PMID:Methylammonium resistance in Aspergillus nidulans. 578 5

The isolation and characterization of mutants altered for nitrate assimilation in Neurospora crassa is described. The mutants isolated can be subdivided into five classes on the basis of growth test that correspond to the growth patterns of existing mutants at six distinct loci. Mutants with growth characteristics like those of nit-2, nit-3 and nit-6 are assigned to those loci on the basis of noncomplementation and lack of recombination. Mutants that, from their growth patterns, appear to lack the molybdenum-containing cofactor for both nitrate reductase and xanthine dehydrogenase subdivide into three loci (nit-y, nit-8 and nit-9), all of which are gentically distinct from nit-1. nit-9 is a complex locus consisting of three complementation groups and thus appears similar ao the cnxABC locus of Asperillus nidulans. Extensive complementational and recombinational analyses reveal that nit-4 and nit-5 are alleles of the same locus, and two new alleles of that locus have been isolated. The results indicate that, as in A. nidulans, nitrate assimilation in N. crassa requires at least four loci (nit-1, 7, 8 and 9) to produce the molybdenum co-factor for nitrate reductase (and xanthine dehydrogenase), one locus (nit-3) to code for the nitrate reductase apoprotein, one locus (nit-6) to code for the nitrite reductase approtein and only one lous (nit-4/5) for the regulation of induction of the pathway by nitrate and nitrite.
 ...
PMID:The isolation and characterization of mutants defective in nitrate assimilation in Neurospora crassa. 644 99

The distribution of the Mo-enzymes aldehyde oxidase (AO; EC 1.2.3.1) xanthine dehydrogenase (XDH; EC 1.2.1.37) and nitrate reductase (NAD(P)H NR; EC 1.6.6.1-2) was studied along the longitudinal and transversal axes of maize (Zea mays L. cv. Jubily) nodal roots as affected by nitrogen sources and salinity. Activities of the Mo-enzymes were considerably enhanced under mild saline conditions. The activities of AO and XDH increased following addition of ammonium to the nutrient solution. Immunoblot analysis with antibodies raised against maize AO protein revealed increased levels of AO proteins in root tips of ammonium fed plants. Application of salinity to nitrate fed plants did not affect the enzyme protein level, although it enhanced the activity of the Mo-hydroxylases. The specific activities of the Mo-enzymes were the highest in root tips (0-1 cm segments) while on the transversal axis maximal activity was observed in the stele or vascular cylinder. Activity staining of AO after native PAGE of root extracts revealed four bands of AO proteins (AO1-4) capable of oxidizing a number of aliphatic and aromatic aldehydes. Increased AO activity in maize nodal roots grown with ammonium, and salinity were observed mainly at the AO3 and AO4 bands. Tips and stele contained primarily AO3 and AO4, and only traces of AO1 and AO2. SDS-PAGE of root extracts followed by Western blots revealed, besides the major 150 kD subunit of AO, two polypeptides with molecular masses of 72 and 85 kD located specifically in the cortex. Part of the polymorphism of AO in plant roots may be related to the allocation of distinct isoforms to different regions of the root, although the specific metabolic roles of the different bands have not been established.
 ...
PMID:Distribution of the Mo-enzymes aldehyde oxidase, xanthine dehydrogenase and nitrate reductase in maize (Zea mays L.) nodal roots as affected by nitrogen and salinity. 1077 39

We examined whether xanthine oxidoreductase (XOR), a hypoxia-inducible enzyme capable of generating reactive oxygen species, is involved in the onset of angiotensin (Ang) II-induced vascular dysfunction in double-transgenic rats (dTGR) harboring human renin and human angiotensinogen genes. In 7-week-old hypertensive dTGR, the endothelium-mediated relaxation of noradrenaline (NA)-precontracted renal arterial rings to acetylcholine (ACh) in vitro was markedly impaired compared with Sprague Dawley rats. Preincubation with superoxide dismutase (SOD) improved the endothelium-dependent vascular relaxation, indicating that in dTGR, endothelial dysfunction is associated with increased superoxide formation. Preincubation with the XOR inhibitor oxypurinol also improved endothelium-dependent vascular relaxation. The endothelium-independent relaxation to sodium nitroprusside was similar in both strains. In dTGR, serum 8-isoprostaglandin F(2alpha), a vasoconstrictor and antinatriuretic arachidonic acid metabolite produced by oxidative stress, was increased by 100%, and the activity of XOR in the kidney was increased by 40%. Urinary nitrate plus nitrite (NO(x)) excretion, a marker of total body NO generation, was decreased by 85%. Contractile responses of renal arteries to Ang II, endothelin-1 (ET-1), and NA were decreased in dTGR, suggesting hypertension-associated generalized changes in the vascular function rather than a receptor-specific desensitization. Valsartan (30 mg/kg PO for 3 weeks) normalized blood pressure, endothelial dysfunction, and the contractile responses to ET-1 and NA. Valsartan also normalized serum 8-isoprostaglandin F(2alpha) levels, renal XOR activity, and, to a degree, NO(x) excretion. Thus, overproduction of Ang II in dTGR induces pronounced endothelial dysfunction, whereas the sensitivity of vascular smooth muscle cells to nitric oxide is unaltered. Ang II-induced endothelial dysfunction is associated with increased oxidative stress and vascular xanthine oxidase activity.
 ...
PMID:Endothelial dysfunction and xanthine oxidoreductase activity in rats with human renin and angiotensinogen genes. 1123 Mar 10

Xanthine oxidoreductase catalyses the anaerobic reduction of glyceryl trinitrate (GTN), isosorbide dinitrate and isosorbide mononitrate to inorganic nitrite using xanthine or NADH as reducing substrates. Reduction rates are much faster with xanthine as reducing substrate than with NADH. In the presence of xanthine, urate is produced in essentially 1:1 stoichiometric ratio with inorganic nitrite, further reduction of which is relatively slow. Organic nitrates were shown to interact with the FAD site of the enzyme. In the course of reduction of GTN, xanthine oxidoreductase was progressively inactivated by conversion to its desulpho form. It is proposed that xanthine oxidoreductase is one of several flavoenzymes that catalyse the conversion of organic nitrate to inorganic nitrite in vivo. Evidence for its further involvement in reduction of the resulting nitrite to nitric oxide is discussed.
 ...
PMID:Reduction of organic nitrates catalysed by xanthine oxidoreductase under anaerobic conditions. 1142 Jan 46

In contrast to its parent strain, transposon Tn5-Mob insertion mutant HB6 of the facultative chemoautotroph Ralstonia eutropha was unable to grow organoautotrophically on formate and exhibited no activity of Mo-dependent, membrane-bound formate dehydrogenase (M-FDH) when cultivated mixotrophically on fructose plus formate. The activity of another molybdoenzyme, the soluble, NAD+-linked formate dehydrogenase which is the key enzyme of formate utilization in R. eutropha, was greatly diminished in the mutant. HB6 also lacked the W-dependent M-FDH activities that were newly discovered in organoautotrophically, lithoautotrophically, or mixotrophically grown wildtype cells. However, an additional W-dependent M-FDH activity, observed in heterotrophically grown stationary-phase cells, was present in the mutant although at a considerably reduced level. Sequence analyses of the complementing chromosomal wildtype and the corresponding mutant DNA fragment revealed the transposon insertion to be located in moeA, a gene involved in the biosynthesis of the molybdopterin cofactor (MoCo). Nevertheless, mutant HB6 was able to grow on xanthine as carbon and energy source and with nitrate as nitrogen source. The utilization of these substrates requires the function of the MoCo-containing enzymes xanthine dehydrogenase and assimilatory nitrate reductase, respectively, that were still active in the mutant. A moeA deletion mutant exhibited the same phenotype as that of HB6. The moeA gene belongs to an unusual mol operon consisting of four genes (moeA, moaD, moaE, and moaF) and being constitutively expressed at low level. Unlike MoeA, the large subunit of molybdopterin synthase encoded by moaE is essential for molybdopterin biosynthesis as was evident by the phenotype of a moaE deletion mutant. MoaF is a novel gene product which showed no similarity to proteins with known function but was indispensable for reconstituting organoautotrophic growth in HB6. The findings suggest that MoeA of R. eutropha is differentially involved in the biosynthesis or incorporation of pterin cofactors of/into the various molybdo- and tungstoenzymes.
 ...
PMID:Involvement of an unusual mol operon in molybdopterin cofactor biosynthesis in Ralstonia eutropha. 1154 79


1 2 3 4 5 6 7 8 Next >>