Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the first patient in Finland and Scandinavia with a deficiency of adenine phosphoribosyltransferase (APRT). About 30 clinically affected patients have been reported in the literature. APRT deficiency is an enzyme disorder which is inherited autosomally in a recessive manner. The use of adenine in purine metabolism is disturbed and it accumulates in the body, where it is oxidised to poorly insoluble 2,8-dihydroxyadenine by xanthine oxidase. The dihydroxyadenine forms stones which can be mistaken for uric acid stones. Our patient had had frequent episodes of urolithiasis and the diagnosis was finally made after pyelolithotomy and stone analysis. The total APRT deficiency was detected in the haemolysate of erythrocytes. Partial deficiency of APRT in the patient's relatives showed heterozygosity of the enzyme defect. The only clinical manifestation of the defect is the formation of urinary stones. This can be prevented by diet and allopurinol.
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PMID:Adenine phosphoribosyltransferase deficiency: 2,8-dihydroxyadenine urolithiasis in a 48-year-old woman. 280 78

We applied a sensitive, precise liquid-chromatographic method of analysis for inosine, hypoxanthine, and xanthine to the study of fructose metabolism in humans and in rats. In the rat, intravenous loading with fructose induced, within minutes, substantial increases in the concentrations of inosine, hypoxanthine, and xanthine in plasma and urine. In plasma, these concentrations peaked after 5 min, then practically disappeared within 10 min. As expected, the fructose-induced increase in hypoxanthine was greatly amplified by pretreating the rats with allopurinol, an inhibitor of xanthine oxidase. In a healthy human subject, intravenous administration of fructose also induced prompt, substantial, and rapidly reversing increases in the concentrations of these metabolites of adenine nucleotides in plasma. The finding that fructose induced almost-immediate increases in the plasma concentrations of inosine, hypoxanthine, and xanthine is consistent with previous studies in rats, in which parenteral administration of fructose induced almost-immediate decreases of total adenine nucleotides (ATP + ADP + AMP) in the liver, and increased concentrations of uric acid and allantoin in the plasma.
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PMID:Liquid-chromatographic measurements of inosine, hypoxanthine, and xanthine in studies of fructose-induced degradation of adenine nucleotides in humans and rats. 369 69

The morphological, biochemical and functional characterization of the vascular endothelium has become possible through the broad use of electron microscopic methods, the successful elaboration and application of techniques for the isolation and cultivation of endothelial cells in vitro and through sophisticated studies on vessel and organ preparations, both in vitro and in vivo. In this survey emphasis is placed on certain methodological aspects of endothelial cell culture as well as on biochemical, physiological and pathophysiological features of the vascular endothelium. Endothelial cells can be propagated in culture dishes, the most commonly applied method, on suspended microbeads (dextrane, polyacrylamide), a technique giving large yields, or on thin porous membranes, a procedure suited for the study of transport processes across the endothelial layer. Different structural, biochemical and functional properties of the luminal (apical) and abluminal (basal) cell membrane determine important polarity features of the endothelium. Endothelial cells exhibit a variety of biochemical pathways and are characterized by high metabolic activities. Of particular interest is the large content of ATP in endothelial cells of different vascular origin. The rapid intracellular degradation of adenine nucleotides to nucleosides and bases, which are constantly released, is balanced by synthesis, mainly via salvage pathways. In endothelial cells of microvascular origin uric acid predominates by far as the final purine degradative because of the presence of xanthine dehydrogenase in these cells; in the macrovascular endothelium purine breakdown proceeds only to hypoxanthine, since xanthine dehydrogenase is lacking. In this connection interrelations between nucleotide catabolism in myocardial tissue and in coronary endothelial cells are discussed, also with respect to the participation of endothelial xanthine oxidase in the formation of oxygen radicals during post-ischemic reperfusion of the heart. Vascular endothelial cells of different origin are also capable of a rapid extracellular degradation of ATP, ADP and AMP to adenosine by means of specific ecto-nucleotidases. The subsequent fate of extracellularly formed adenosine appears to be different for endothelial cells of microvascular (preferential adenosine uptake) and macrovascular origin (preferential extracellular adenosine accumulation), thus implying functional consequences for platelet aggregation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The vascular endothelium: a survey of some newly evolving biochemical and physiological features. 393 1

1. Allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) selectively inhibits the apotryptophan pyrrolase activity in homogenates of rat liver in vitro and after intraperitoneal administration. The inhibition is abolished by an excess of haematin. The allopurinol metabolite alloxanthine has no effect on the pyrrolase activity in vitro or after administration. Allopurinol also inhibits the activation of the enzyme in vitro by ascorbate, ethanol plus NAD(+), NADH, hypoxanthine or xanthine. It is suggested that these agents cause the conversion of a latent form of the pyrrolase into the apoenzyme, and that xanthine oxidase is not involved in this process. 2. The raised total pyrrolase activity observed after the administration of cortisol, cyclic AMP, tryptophan, salicylate or ethanol is lowered by allopurinol in vitro to the corresponding holoenzyme values. A similar effect is observed when allopurinol is administered shortly before cortisol or cyclic AMP. Pretreatment of rats with allopurinol completely prevents the enhancement of the pyrrolase activities by tryptophan, salicylate or ethanol. 3. It is suggested that allopurinol inhibits rat liver tryptophan pyrrolase activity in vitro and after administration by preventing the conjugation of the apoenzyme with its haem activator. The possible usefulness of combined allopurinol-tryptophan therapy of affective disorders is discussed.
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PMID:The mechanism of inhibition of rat liver tryptophan pyrrolase activity by 4-hydroxypyrazolo(3,4-d)pyrimidine (Allopurinol). 435 41

The origin of luminol-dependent chemiluminescence (CL) in neutrophils stimulated by immune complexes (IC) was investigated. It was found that CL induced by soluble IC and aggregated human gamma globulin (AHG) was glucose-independent, while insoluble IC-induced CL was diminished in the absence of glucose. AHG-induced CL was not inhibited by superoxide dismutase, catalase or 2,5-dimethyl furan, but was suppressed in the presence of phenol, sodium benzoate, sodium formate and mannitol. The CL was also inhibited by inhibitors of arachidonic acid (AA) metabolism including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin and aspirin, and by prostaglandins E1 and E2, theophylline and dibutyryl cyclic AMP. Luminol-dependent CL was also studied in cell-free systems including AA plus soybean lipoxygenase, hydroperoxyeicosatetraenoic acid plus peroxidase and xanthine oxidase plus xanthine. Our results indicate that, in neutrophils exposed to soluble IC and AHG, CL is produced and this is closely linked to the formation of free radicals during the metabolism of AA. The radical(s) involved is likely to include the hydroxyl radical. In neutrophils stimulated by large aggregates of IC or micro-organisms, superoxide anion, H2O2 and singlet oxygen are also produced as a result of activation of NAD(P)H oxidase. These oxygen species function as oxidizing agents for AA metabolism and amplify the production of hydroxyl radical along the lipoxygenase (and possibly cyclooxygenase) pathway(s).
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PMID:Luminol-dependent chemiluminescence produced by neutrophils stimulated by immune complexes. 608 70

In the present study we examined the effect of reactive oxygen metabolites (generated by the xanthine-xanthine oxidase system), on adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanosine-3',5'-cyclic monophosphate (cyclic GMP) content in glomeruli and tubules that were isolated from rat renal cortex. Xanthine (0.1 mM)-xanthine oxidase (0.025 U/ml) significantly increased (P less than 0.001) the cyclic AMP content in glomeruli from 18 +/- 1 to 50 +/- 4 pmol/mg protein (n = 13). The response was dose dependent and was markedly inhibited (delta %-74 +/- 9, n = 3) by allopurinol (10(-3), a specific inhibitor of xanthine oxidase. Cyclic AMP content in the tubules, and the cyclic GMP content in glomeruli and tubules, were not altered by the xanthine-xanthine oxidase system. This lack of response was not due to lack of responsiveness of the tissues because parathyroid hormone caused a marked increase in the cyclic AMP content in tubules, and nitroprusside markedly increased the cyclic GMP content in glomeruli. The increase in cyclic AMP in glomeruli was due to generation of reactive oxygen metabolites rather than of other products (e.g. uric acid) of the xanthine-xanthine oxidase reaction--addition of uric acid to incubations had no effect; using another substrate for xanthine oxidase, acetaldehyde significantly increased (delta % 112 +/- 7, n = 4, P less than 0.001) the cyclic AMP content; and catalase that destroys hydrogen peroxide caused a marked inhibition (delta % -90 +/- 5, n = 4) of the response to xanthine-xanthine oxidase. The marked inhibition by catalase, and the lack of effect of superoxide dismutase (in a concentration that completely scavenged superoxide) suggested hydrogen peroxide as the responsible oxygen metabolite for the observed effect. Glucose-glucose oxidase (a system that directly generates hydrogen peroxide), and direct addition of hydrogen peroxide caused a dose-dependent increase in the cyclic AMP content in glomeruli, which further supports the role of hydrogen peroxide as the responsible species for the observed effect. Additional experiments that used prostaglandin synthesis inhibitors and antagonists of serotonin and histamine suggested that hydrogen peroxide increases cyclic AMP content in glomeruli by enhancing prostaglandin synthesis.
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PMID:Effect of enzymatically generated reactive oxygen metabolites on the cyclic nucleotide content in isolated rat glomeruli. 608 13

Regional intestinal ischemia in cats resulted in an accumulation of hypoxanthine within 2 h, the concentration of which rose from 0.062 to 1.131 nmol/mg protein. A similar rise in AMP content (from 0.5 to 3.2 nmol/mg protein) was observed, but not in the ADP level. In parallel, ATP content decreased from 7.5 to 2.8 nmol/mg protein. Reperfusion of the ischemic tissue was followed by rapid metabolism of the purine metabolites; after 1 h of reperfusion the tissue level of hypoxanthine was 0.186 nmol/mg protein, of AMP 0.7 nmol/mg protein, and of ATP 4.3 nmol/mg protein. The oxidation of hypoxanthine, mediated by xanthine oxidase, is accompanied by the release of superoxide ions. Consequently, the concentration of oxidized glutathione was doubled upon reperfusion, while marked lipid peroxidation took place, as evidenced by the rise in conjugated diene content from 2.8 mumol/g tissue before reperfusion to 5.6 mumol/g tissue after 10 min of reoxygenation. In line with these findings is the fact that histologically observable damage occurred mainly in the presence of oxygen. These data indicate that, at least in our model, rapid reoxygenation is a major cause of "ischemic" tissue damage.
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PMID:Oxidative tissue damage following regional intestinal ischemia and reperfusion in the cat. 609 11

Uninduced rat liver microsomes and NADPH-Cytochrome P-450 reductase, purified from phenobarbital-treated rats, catalyzed an NADPH-dependent oxidation of hydroxyl radical scavenging agents. This oxidation was not stimulated by the addition of ferric ammonium sulfate, ferric citrate, or ferric-adenine nucleotide (AMP, ADP, ATP) chelates. Striking stimulation was observed when ferric-EDTA or ferric-diethylenetriamine pentaacetic acid (DTPA) was added. The iron-EDTA and iron-DTPA chelates, but not unchelated iron, iron-citrate or iron-nucleotide chelates, stimulated the oxidation of NADPH by the reductase in the absence as well as in the presence of phenobarbital-inducible cytochrome P-450. Thus, the iron chelates which promoted NADPH oxidation by the reductase were the only chelates which stimulated oxidation of hydroxyl radical scavengers by reductase and microsomes. The oxidation of aminopyrine, a typical drug substrate, was slightly stimulated by the addition of iron-EDTA or iron-DTPA to the microsomes. Catalase inhibited potently the oxidation of scavengers under all conditions, suggesting that H2O2 was the precursor of the hydroxyl radical in these systems. Very high amounts of superoxide dismutase had little effect on the iron-EDTA-stimulated rate of scavenger oxidation, whereas the iron-DTPA-stimulated rate was inhibited by 30 or 50% in microsomes or reductase, respectively. This suggests that the iron-EDTA and iron-DTPA chelates can be reduced directly by the reductase to the ferrous chelates, which subsequently interact with H2O2 in a Fenton-type reaction. Results with the reductase and microsomal systems should be contrasted with results found when the oxidation of hypoxanthine by xanthine oxidase was utilized to catalyze the production of hydroxyl radicals. In the xanthine oxidase system, ferric-ATP and -DTPA stimulated oxidation of scavengers by six- to eightfold, while ferric-EDTA stimulated 25-fold. Ferric-desferrioxamine consistently was inhibitory. Superoxide dismutase produced 79 to 86% inhibition in the absence or presence of iron, indicating an iron-catalyzed Haber-Weiss-type of reaction was responsible for oxidation of scavengers by the xanthine oxidase system. These results indicate that the ability of iron to promote hydroxyl radical production and the role that superoxide plays as a reductant of iron depends on the nature of the system as well as the chelating agent employed.
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PMID:The role of iron chelates in hydroxyl radical production by rat liver microsomes, NADPH-cytochrome P-450 reductase and xanthine oxidase. 633 21

The luminol-dependent chemiluminescence (CL) of neutrophils phagocytosing zymosan is inhibited by superoxide dismutase (SOD), catalase, sodium benzoate, and 2,5-dimethyl furan. In the present report it is shown that inhibition by SOD and 2,5-dimethyl furan is diminished and removed, respectively, by the omission of glucose from the incubation medium. Zymosan-induced CL is also inhibited by inhibitors of arachidonic acid (AA) metabolism, including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin, and aspirin, by prostaglandins E1 and E2, theophylline, and dibutyryl cyclic AMP (cAMP), and by the addition of AA, sodium fluoride, and xanthine oxidase plus xanthine to the cell suspension. These findings lead us to postulate that the metabolism of AA via the lipoxygenase (and cyclooxygenase) pathway(s) is the source of CL observed in neutrophils after phagocytosis. Reactive oxygen species produced as a result of activation of NAD(P)H oxidase provide oxidizing agents for the oxidation of AA along these pathways. It is also suggested that elevated levels of cAMP induced by prostaglandins synthesized via the cyclooxygenase pathway may play a role in the regulation of the zymosan-induced CL response.
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PMID:The origin of chemiluminescence produced by neutrophils stimulated by opsonized zymosan. 668 3

In the ischemic heart, high-energy phosphates are rapidly broken down. We studied the release of AMP catabolites from the isolated perfused rat heart which was temporarily made ischemic or anoxic. We measured the concentration of purine nucleosides and oxypurines with a novel high-pressure liquid chromatographic technique. The postischemic working heart released adenosine, inosine, hypoxanthine, and also substantial amounts of xanthine. The latter could indicate that xanthine oxidase is present in rat heart. Further evidence for the myocardial occurrence of this enzyme was obtained from experiments with hearts perfused retrogradely with allopurinol, an inhibitor of xanthine oxidase. This drug greatly enhanced the release of hypoxanthine, both during normoxic and anoxic perfusions. We conclude that xanthine oxidase could play an essential role in the myocardial breakdown of AMP catabolites.
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PMID:Release of purine nucleosides and oxypurines from the isolated perfused rat heart. 668 47


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