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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of the vasodilator, hydralazine, with the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase has been investigated. A potent progressive inhibition of rabbit liver aldehyde oxidase, in the presence of substrate, by low concentrations of hydralazine (0.1-1 microM) was observed in vitro but no effect was seen with bovine milk xanthine oxidase. This activity was mirrored in vivo when levels of aldehyde oxidase were significantly decreased in rabbits administered hydralazine (10 mg/kg/day for seven days) whereas hepatic xanthine oxidase activity was unaltered by hydralazine treatment. Various metabolites of hydralazine were synthesized but found to be devoid of in vitro inhibitory activity. Aldehyde oxidase prepared from either guinea pig or baboon liver was inhibited in a similar way to that of rabbit liver.
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PMID:Hydralazine: a potent inhibitor of aldehyde oxidase activity in vitro and in vivo. 384 Oct

Isoelectric focusing and electrophoresis were used to identify the various isozymes of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aldehyde oxidase (AOX), and xanthine oxidase (XOX). ADH types I, II, and III were located primarily in the cytosol fraction of liver, but some activity was found also in the small granule fraction. The ALDH-I and -IV isozymes were found in the large granule fraction, while ALDH-II and -III were present in the cytosol and ALDH-V in the small granule fraction. AOX and XOX each appeared as a single cytosolic form with some small granule activity. The tissue distribution of these isozymes is presented and the physiological role of each enzyme is discussed.
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PMID:Analysis of human alcohol- and aldehyde-metabolizing isozymes by electrophoresis and isoelectric focusing. 389 98

The sensitivity of cultured L1210 and P388 cells sensitive (L1210/0, P388/0) and resistant (L1210/OAP, P388/CLA) to oxazaphosphorines, to 4-hydroperoxycyclophosphamide, ASTA Z-7557, phosphoramide mustard, and acrolein was determined in the absence and presence of known (disulfiram, diethyldithiocarbamate, cyanamide) or suspected [ethylphenyl(2-formylethyl)phosphinate] inhibitors of aldehyde dehydrogenase activity. The L1210/OAP cell line is resistant specifically to the oxazaphosphorines; P388/CLA cells are partially cross-resistant to other cross-linking agents. All four inhibitors of aldehyde dehydrogenase activity potentiated the cytotoxic action of the oxazaphosphorines, 4-hydroperoxycyclophosphamide and ASTA Z-7557, against L1210/OAP and P388/CLA cells; in the presence of a sufficient amount of inhibitor, sensitivity was essentially fully restored in both cases. The inhibitors did not potentiate the cytotoxic action of the nonoxazaphosphorines, phosphoramide mustard and acrolein, against these cell lines. The cytotoxic action of the oxazaphosphorines and nonoxazaphosphorines against L1210/0 and P388/0 cells was not potentiated by any of the aldehyde dehydrogenase inhibitors. Inhibitors of xanthine oxidase or aldehyde oxidase activities did not potentiate the cytotoxic action of the oxazaphosphorines against L1210/OAP cells. These observations strongly suggest that (a) aldehyde dehydrogenase activity is an important determinant with regard to the sensitivity of a cell population to the oxazaphosphorines; (b) L1210/0 and P388/0 cells lack the relevant aldehyde dehydrogenase activity; (c) the phenotypic basis for the resistance to oxazaphosphorines by L1210/OAP cells is aldehyde dehydrogenase activity; and (d) the major reason that P388/CLA cells are resistant to oxazaphosphorines is aldehyde dehydrogenase activity.
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PMID:Restoration of sensitivity to oxazaphosphorines by inhibitors of aldehyde dehydrogenase activity in cultured oxazaphosphorine-resistant L1210 and cross-linking agent-resistant P388 cell lines. 397 23

Isoelectric focusing techniques (IEF) were used to examine the tissue distribution and genetic variability of aldehyde dehydrogenases (AHDs) from inbred strains of mice. Twelve zones of AHD activity were resolved which were differentially distributed between tissues. Liver extracts exhibited highest activity for most enzymes, with the exception of isozymes found in stomach (AHD-4) and testis (AHD-4 and AHD-6). Genetic variants for AHD-1 (liver mitochondrial isozyme) and AHD-4 (stomach isozyme) were examined from inbred strains and F1 hybrid animals. The results were consistent with dimeric subunit structures (designated as A2 and D2 isozymes respectively). IEF patterns for activity variants of testis-specific AHD-6 were identical, with 3-banded phenotypes being observed. pI values for the AHD forms as well as for aldehyde oxidase and xanthine oxidase isozymes, which stain in the absence of coenzyme, were reported.
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PMID:Isoelectric focusing studies of aldehyde dehydrogenases from mouse tissues: variant phenotypes of liver, stomach and testis isozymes. 404 Aug 41

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.
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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

The reactions catalyzed by Mo enzymes each find the product differing from the substrate by two electrons and two protons (or some multiple thereof). The coordination chemistry of Mo suggests that there is a distinct relationship between acid-base and redox properties of Mo complexes, and that a coupled electron-proton transfer (to or from substrate) may be mediated by Mo in enzymes. Each of the Mo enzymes (nitrogenase, nitrate reductase, xanthine oxidase, aldehyde oxidase, and sulfite oxidase) is discussed; it is shown that a simple molecular mechanism embodying coupled proton-electron transfer can explain many key experimental observations. In view of this mechanism, the reasons for the use of Mo (from an evolutionary and chemical point of view) are discussed and other metals that may replace Mo are considered.
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PMID:Proposed molecular mechanism for the action of molybedenum in enzymes: coupled proton and electron transfer. 451 30

The present paper describes that mammalian liver aldehyde oxidase is involved in the reduction of nicotinamide N-oxide to nicotinamide. Rabbit liver aldehyde oxidase supplemented with its electron donor exhibited a significant nicotinamide N-oxide reductase activity under anaerobic conditions. Liver cytosols from rabbits, hogs, guinea pigs, hamsters, rats and mice, all of them, similarly exhibited the N-oxide reductase activity in the presence of an electron donor of aldehyde oxidase, but not xanthine oxidase. The cytosolic N-oxide reductase activity was almost completely inhibited by menadione, an inhibitor of aldehyde oxidase.
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PMID:Involvement of liver aldehyde oxidase in the reduction of nicotinamide N-oxide. 623 71

The reduced forms of xanthine oxidase, xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase are inactivated by cyanide. Following gel filtration to remove excess of reductant and cyanide, the isolated enzymes remain inactive. Thiocyanate, a product of inactivation of the oxidized forms of the xanthine- and aldehyde-oxidizing enzymes by cyanide, is not released during inactivation of the reduced enzymes. Studies with [14C]cyanide show that, while stoichiometric binding is required for the onset of inactivation, its continued binding is not essential to maintenance of the inactivated state. Electron paramagnetic resonance and absorption spectroscopic studies on the isolated inactivated enzymes show that prosthetic groups other than molybdenum are fully oxidized but that the molybdenum centers are modified. Reactivation is accomplished by incubation with suitable oxidants. Aerobic reactivation of inactive sulfite oxidase required only 1 eq of ferricyanide/active site. However, under rigorously anaerobic conditions, 3 to 4 mol of ferricyanide/active site were reduced, indicating that the molybdenum centers in the inactive enzyme had been reduced below the levels attained by the native enzyme during catalysis.
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PMID:Mechanisms of inactivation of molybdoenzymes by cyanide. 624 90

Activation of the desulfo forms of milk xanthine oxidase, chicken liver xanthine dehydrogenase, and aldehyde oxidase with S2- is greatly facilitated in the presence of reducing agents. Upon anaerobic incubation with 1 mM S2- and 1 mM dithionite, desulfo xanthine oxidase and chicken liver xanthine dehydrogenase prepared by cyanide treatment of active enzymes, are activated to the specific activity predicted by their molybdenum content. Routine preparations containing desulfo molecules are also similarly activated to the extent predicted. Cyanide-inactivated chicken liver xanthine dehydrogenase was reconstituted with 35S2- in the presence of dithionite. 85% of enzyme-bound radioactivity was shown to be in the form of cyanolyzable sulfur, by comparison of enzyme activity, bound radioactivity, and 35SCN- yields from exposure of labeled enzyme to cyanide. This radiolabeled enzyme allowed the determination of the following. 1) The cyanolyzable sulfur is largely removed from the polypeptide by incubation at 37 degrees C for one hour in 1% sodium dodecyl sulfate, pH 7, or for 15 min in 6 M guanidinium chloride, pH 6.2. 2) The cyanolyzable sulfur is "acid labile." [35S]Methylene blue is formed in the theoretical quantity from oxidized or substrate-reduced enzyme under the standard conditions for labile sulfur analysis by the methylene blue method. These data strongly support the conclusion that the cyanolyzable sulfur is a terminal sulfur ligand of the Mo atom, and is not part of an organic moiety.
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PMID:Evidence for the inorganic nature of the cyanolyzable sulfur of molybdenum hydroxylases. 627 83

Molybdenum(V) e.p.r. spectra from reduced forms of aldehyde oxidase were obtained and compared with those from xanthine oxidase. Inhibited and Desulpho Inhibited signals from aldehyde oxidase were fully characterized, and parameters were obtained with the help of computer simulations. These differ slightly but significantly from the corresponding parameters for the xanthine oxidase signals. Rapid type 1 and type 2 and Slow signals were obtained from aldehyde oxidase, but were not fully characterized. From the general similarities of the signals from the two enzymes, it is concluded that the ligands of molybdenum must be identical and that the overall co-ordination geometries must be closely similar in the enzymes. The striking differences in substrate specificity must relate primarily to structural differences in a part of the active centre concerned with substrate binding and not involving the catalytically important molybdenum site.
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PMID:Studies by electron-paramagnetic-resonance spectroscopy of the molybdenum centre of aldehyde oxidase. 628 95


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