Phylogeny and correlations of aldehyde oxidase, xanthine oxidase, xanthine dehydrogenase and peroxidase in animal tissues.
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Aldehyde Oxidoreductases↗
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Metabolism of isovanillin by aldehyde oxidase, xanthine oxidase, aldehyde dehydrogenase and liver slices.
Aromatic aldehydes are good substrates of aldehyde dehydrogenase activity but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. However, the oxidation of xenobiotic-derived aromatic aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase and xanthine oxidase activities in the oxidation of isovanillin in separate preparations and also in freshly prepared and cryopreserved liver slices. The oxidation of isovanillin was also examined in the presence of specific inhibitors of each oxidizing enzyme. Minimal transformation of isovanillin to isovanillic acid was observed in partially purified aldehyde oxidase, which is thought to be due to residual xanthine oxidase activity. Isovanillin was rapidly metabolized to isovanillic acid by high amounts of purified xanthine oxidase, but only low amounts are present in guinea pig liver fraction. Thus the contribution of xanthine oxidase to isovanillin oxidation in guinea pig is very low. In contrast, isovanillin was rapidly catalyzed to isovanillic acid by guinea pig liver aldehyde dehydrogenase activity. The inhibitor studies revealed that isovanillin was predominantly metabolized by aldehyde dehydrogenase activity. The oxidation of xenobiotic-derived aromatic aldehydes with freshly prepared or cryopreserved liver slices has not been previously reported. In freshly prepared liver slices, isovanillin was rapidly converted to isovanillic acid, whereas the conversion was very slow in cryopreserved liver slices due to low aldehyde dehydrogenase activity. The formation of isovanillic acid was not altered by allopurinol, but considerably inhibited by disulfiram. It is therefore concluded that isovanillin is predominantly metabolized by aldehyde dehydrogenase activity, with minimal contribution from either aldehyde oxidase or xanthine oxidase.
Aldehyde Dehydrogenase↗
[Xanthine oxidase (xanthine dehydrogenase)].
Xanthine oxidase (xanthine dehydrogenase) is composed of two identical subunits of approximately 150,000 daltons. Each subunit contains four oxdation-reduction active cofactors/monomers. In vivo, the enzyme exists mostly as the dehydrogenase type (the NAD-dependent type). The cDNA has been cloned from human liver, and the amino acid sequence has been determined. As xanthine oxidase seems to produce superoxide in postischemic reperfusion, the relation between the superoxide and postischemic tissue injury has been discussed. It has also been reported that inhibition of xanthine oxidase by allopurinol may cause severe 6-mercaptopurine toxicity.
DNA↗
Contribution of aldehyde oxidase, xanthine oxidase, and aldehyde dehydrogenase on the oxidation of aromatic aldehydes.
Aliphatic aldehydes have a high affinity toward aldehyde dehydrogenase activity but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. In addition, the oxidation of xenobiotic-derived aromatic aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase, and xanthine oxidase activities in the oxidation of substituted benzaldehydes in separate preparations. The incubation of vanillin, isovanillin, and protocatechuic aldehyde with either guinea pig liver aldehyde oxidase, bovine milk xanthine oxidase, or guinea pig liver aldehyde dehydrogenase demonstrated that the three aldehyde oxidizing enzymes had a complementary substrate specificity. Incubations were also performed with specific inhibitors of each enzyme (isovanillin for aldehyde oxidase, allopurinol for xanthine oxidase, and disulfiram for aldehyde dehydrogenase) to determine the relative contribution of each enzyme in the oxidation of these aldehydes. Under these conditions, vanillin was rapidly oxidized by aldehyde oxidase, isovanillin was predominantly metabolized by aldehyde dehydrogenase activity, and protocatechuic aldehyde was slowly oxidized, possibly by all three enzymes. Thus, aldehyde oxidase activity may be a significant factor in the oxidation of aromatic aldehydes generated from amines and alkyl benzenes during drug metabolism. In addition, this enzyme may also have a role in the catabolism of biogenic amines such as dopamine and noradrenaline where 3-methoxyphenylacetic acids are major metabolites.
Aldehyde Dehydrogenase↗
Studies on xanthine oxidase: Xanthine oxidase and lactoflavine.
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Journal Article↗
Short-term acetaldehyde exposure depresses ventricular myocyte contraction: role of cytochrome P450 oxidase, xanthine oxidase, and lipid peroxidation.
BACKGROUND: Chronic alcoholism leads to the development of alcoholic cardiomyopathy, manifested as ventricular dilation and impaired ventricular contractility. However, the specific toxic mechanism responsible for alcoholic cardiomyopathy remains unclear. One major candidate toxin is the first metabolic product of ethanol, acetaldehyde (ACA). This study was designed to examine the role of cytochrome P450 oxidase 2E1 (CYP 2E1), xanthine oxidase, and lipid peroxidation in the short-term ACA exposure-induced mechanical defects in adult rat ventricular myocytes. METHODS: Mechanical and intracellular Ca2+ properties were evaluated by an IonOptix SoftEdge system. Lipid peroxidation was assessed with malondialdehyde levels by using high-performance liquid chromatography. RESULTS: Short-term (4- to 6-hr) culture of myocytes with ACA (1-100 microM) in sealed containers with silicone septum depressed cell-shortening amplitude, maximal velocity of shortening/relengthening, and prolonged duration of relengthening, as well as intracellular Ca2+ clearing without any effect on the duration of shortening and electrically stimulated an intracellular Ca2+ increase. It is interesting to note that the ACA-induced effects on myocyte mechanical properties were abolished with co-treatment of the lipid peroxidation inhibitor butylated hydroxytoluene (20 microM), the CYP 2E1 inhibitor diallyl sulfide (100 microM), and the xanthine oxidase inhibitor allopurinol (100 microM). Short-term incubation of ACA with the myocytes also produced a significant increase of the lipid peroxidation end product malondialdehyde, which may be prevented by butylated hydroxytoluene. CONCLUSIONS: Collectively, these data provided evidence that ACA depressed cardiomyocyte mechanical function at micromolar levels, possibly through mechanisms related to CYP oxidase, xanthine oxidase, and lipid peroxidation.
Acetaldehyde↗
[Xanthine oxidase--xanthines as a system of endogenous regulation of phosphodiesterase activity].
The paper is concerned with the data indicating close interaction between xanthinoxidase (Xase) and phosphodiesterase (PDE). PDE activity can be modified by affecting the activity of Xase. This effect is mediated by changes in the concentrations of endogenous xanthines. The action of PDE inhibitors, methylxanthines, is discussed from the point of view of the above effect. The data obtained hold promise for purposeful monitoring of tissue concentrations of the cyclic nucleotides in vivo and in vitro.
Allopurinol↗
Electron paramagnetic resonance and potentiometric studies of arsenite interaction with the molybdenum centers of xanthine oxidase, xanthine dehydrogenase, and aldehyde oxidase: a specific stabilization of the molybdenum(V) oxidation state.
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Aldehyde Oxidase↗
Characterization of the molybdenum cofactor of sulfite oxidase, xanthine, oxidase, and nitrate reductase. Identification of a pteridine as a structural component.
The molybdenum cofactor has been isolated in an oxidized inactive form from purified molybdoenzymes. The isolated material is shown to be a novel pterin. The active cofactor is presumably composed of molybdenum and a reduced form of the pterin.
Animals↗
Hydroxyl radical is not a product of the reaction of xanthine oxidase and xanthine. The confounding problem of adventitious iron bound to xanthine oxidase.
The reaction of xanthine and xanthine oxidase generates superoxide and hydrogen peroxide. In contrast to earlier works, recent spin trapping data (Kuppusamy, P., and Zweier, J.L. (1989) J. Biol. Chem. 264, 9880-9884) suggested that hydroxyl radical may also be a product of this reaction. Determining if hydroxyl radical results directly from the xanthine/xanthine oxidase reaction is important for 1) interpreting experimental data in which this reaction is used as a model of oxidant stress, and 2) understanding the pathogenesis of ischemia/reperfusion injury. Consequently, we evaluated the conditions required for hydroxyl radical generation during the oxidation of xanthine by xanthine oxidase. Following the addition of some, but not all, commercial preparations of xanthine oxidase to a mixture of xanthine, deferoxamine, and either 5,5-dimethyl-1-pyrroline-N-oxide or a combination of alpha-phenyl-N-tert-butyl-nitrone and dimethyl sulfoxide, hydroxyl radical-derived spin adducts were detected. With other preparations, no evidence of hydroxyl radical formation was noted. Xanthine oxidase preparations that generated hydroxyl radical had greater iron associated with them, suggesting that adventitious iron was a possible contributing factor. Consistent with this hypothesis, addition of H2O2, in the absence of xanthine, to "high iron" xanthine oxidase preparations generated hydroxyl radical. Substitution of a different iron chelator, diethylenetriaminepentaacetic acid for deferoxamine, or preincubation of high iron xanthine oxidase preparations with chelating resin, or overnight dialysis of the enzyme against deferoxamine decreased or eliminated hydroxyl radical generation without altering the rate of superoxide production. Therefore, hydroxyl radical does not appear to be a product of the oxidation of xanthine by xanthine oxidase. However, commercial xanthine oxidase preparations may contain adventitious iron bound to the enzyme, which can catalyze hydroxyl radical formation from hydrogen peroxide.
Animals↗
Effect of anti-inflammatory drugs on xanthine oxidase and xanthine oxidase induced depolymerization of hyaluronic acid.
The inhibitory effect of various anti-inflammatory drugs on the xanthine oxidase derived depolymerization of hyaluronic acid was studied. The depolymerization was assayed by repeated viscosity measurements. By using a low xanthine oxidase activity, the decrease in viscosity with time followed first order reaction kinetics and was therefore suitable for kinetic analysis. The xanthine oxidase activity was monitored by assay of O2-consumption with a Clark-electrode and by assay of urate production. We present evidence that salicylic, acetylsalicylic, gentisic and azodisalicylic acid and sulfasalazine inhibit the production of oxygen-derived free radicals by xanthine oxidase. We found that sulfapyridine, 5-aminosalicylic acid, allopurinol, mannitol, glucuronic acid and N-acetylglucosamine in addition to the earlier studied drugs, paracetamol, ibuprofen, benoxaprofen and gentisic acid exert their effect via scavenging of free radicals. These drugs had very little effect on the enzyme activity.
Anti-Inflammatory Agents↗
A simple and sensitive method for the activity staining of xanthine oxidase.
Xanthine oxidase is a commercially-important enzyme. Several biochemical compounds have been quantitated by xanthine oxidase. Xanthine oxidase has been used as an auxiliary enzyme in the staining of several enzymes or tissues, however, there is no direct staining method available for it, on polyacrylamide gels. Partially-purified xanthine oxidase from cow milk was used as the enzyme source for the development of an activity-staining method on polyacrylamide gels. Staining was very sensitive. Detection of 0.02 microU of the enzyme on polyacrylamide gels was possible. Staining of 0.05 microU takes about 1 min whereas staining of 0.5 microU will take less than 5 s. Addition of TEMED is not essential for activity staining but it did increase both the rate and the intensity of the staining. The stained gels must be washed with distilled water, extensively, in order to remove excess unoxidized nitroblue tetrazolium, and must be protected from light, for a clear background and sharp activity-band staining. This method might be useful for quality control of xanthine oxidase obtained from different sources.
Animals↗
Superoxide-independent platelet response to xanthine oxidase.
Xanthine oxidase (1--5 microgram/ml) from cow's milk induces shape change, aggregation, and the release reaction of human washed platelets. Xanthine oxidase plus xanthine produce superoxide radicals, which reduce nitro blue tetrazolium. Superoxide dismutase, allopurinol, or ommission of xanthine inhibits the reduction of nitro blue tetrazolium but has no influence on the platelet response to xanthine oxidase. In contrast, small amounts of plasma or apyrase from potatoes abolish the effect on platelets, but not the enzyme activity of xanthine oxidase. Comparison of two xanthine oxidase preparations shows that higher specific enzyme activity corresponds to a lesser effect on platelets. The results suggest that platelet and enzyme activities reside in different components of xanthine oxidase preparations.
Apyrase↗
Purification and immunohistochemical tissue localization of human xanthine oxidase.
Xanthine oxidase was purified 1600-fold from human liver cytosol. The purified enzyme was shown as a single band of 300 kDa on polyacrylamide gel electrophoresis and 150 kDa on SDS-PAGE. Using this purified enzyme, polyclonal antibody against xanthine oxidase was raised in a rabbit. On Ouchterlony's double immunodiffusion method, the raised antibody and the human liver cytosol made a precipitation line stained by activity stain and protein stain, respectively. With the raised anti-xanthine oxidase sera, the immunohistochemical localization of xanthine oxidase in human tissues was examined. Immunostaining of frozen hepatic tissue section showed that the cytoplasm of hepatocytes and endothelial lining cells were stained. In a number of other tissues, the xanthine oxidase antigen was detected only in the endothelial lining cells from heart, kidney, brain, aorta, lung and mesentery, except for the duodenal mucosa cells. A possible role for xanthine oxidase in the endothelial cells from various human tissues in the pathogenesis of reperfusion injury was suggested.
Antibody Specificity↗
Vitamin E deficiency: immunochemical evidence for increased accumulation of liver xanthine oxidase.
Xanthine oxidase (EC 1.2.3.2) activity increases in liver of rabbits deficient in vitamin E. Immunochemical titration of the enzyme demonstrates that the elevation of activity is due to an increased accumulation of the enzyme protein rather than activation of preexisting enzyme molecules. Immunochemically, xanthine oxidase from deficient animals is indistinguishable from the enzyme from control animals. Incorporation of labeled leucine into immunoprecipitable xanthine oxidase is enhanced in vitamin E-deficient animals. This enhancement is interpreted as indicating that the accumulation of xanthine oxidase molecules reflects an accelerated de novo synthesis of the enzyme.
Animals↗
Utilization of riboflavin homologues by D-amino acid oxidase and xanthine oxidase.
D-Amino acid oxidase and xanthine oxidase, two enzymes possessing ionically bound flavin coenzymes have been studied with their flavin coenzymes derived from either 7-ethyl-8-methyl-flavin or 7-methyl-8-ethyl-flavin, vitamin-like homologues of riboflavin. 7-Ethyl-8-methyl-flavin caused a significant reduction of both D-amino acid oxidase and xanthine oxidase in the liver, but not in the kidney. 7-Methyl-8-ethyl-flavin caused a significant reduction of D-amino acid oxidase in both the liver and kidney, a significant reduction of xanthine oxidase in the liver, but a large and significant increase of the latter enzyme in the kidney. An improved procedure for the assay of xanthine oxidase has been described.
Animals↗
The molybdenum centers of xanthine oxidase and xanthine dehydrogenase. Determination of the spectral change associated with reduction from the Mo(VI) to the Mo(IV) state.
The UV-visible absorbance change associated with reduction of the molybdenum centers of xanthine oxidase and xanthine dehydrogenase has been determined using a double-difference technique. At pH 8.5, the Mo(VI) minus Mo(IV) difference spectrum seen with xanthine oxidase exhibits a positive feature at 420 nm, having an extinction change of approximately 3,000 M-1 cm-1 as well as evidence for a negative feature below 340 nm. In xanthine oxidase this change is found to exhibit a marked pH dependence, implicating protonation/deprotonation events associated with changes in the molybdenum oxidation state. Application of the double-difference protocol to the respective circular dichroism spectra of xanthine oxidase and xanthine dehydrogenase reveals appreciable CD changes at 420 and 580 nm associated with the reduction of the molybdenum center. The present results demonstrate a direct spectroscopic handle on the molybdenum centers of both xanthine oxidase and xanthine dehydrogenase.
Animals↗
[The antimicrobial action of the xanthine oxidase-xanthine system on the causative agent of cholera].
As revealed in experiments on V. cholerae, the enzymatic link xanthine oxidase-xanthine produces a vibriostatic effect at the concentration of xanthine oxidase equal to 0.0125 g/l and a vibriocidal effect at the concentration of xanthine oxidase equal to 0.025 g/l in a medium with pH 7.5-7.6. In the presence of protein the antivibrionic activity of the xanthine oxidase link is decreased. The introduction of bivalent iron into the enzymatic link xanthine oxidase-xanthine enhances its vibriocidal action on V. cholerae.
Animals↗