Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 4-year-old patient is described with hyperphenylalaninemia, severe retardation in development, severe muscular hypotonia of the trunk and hypertonia of the extremities, convulsions, and frequent episodes of hyperthermia without infections. Urinary excretion of neopterin, biopterin, pterin, isoxanthopterin, dopamine, and serotonin was very low, although the relative proportions of pterins were normal. In lumbar cerebrospinal fluid, homovanillic acid, 5-hydroxyindoleacetic acid, neopterin and biopterin were low. Oral administration of L-erythro tetrahydrobiopterin normalized the elevated serum phenylalanine within 4 h, serum tyrosine was increased briefly and serum alanine and glutamic acid for a longer time. Urinary dopamine and serotonin excretion were also increased. Administration of an equivalent dose of D-erythro tetrahydroneopterin was ineffective and demonstrated that this compound is not a cofactor in vivo and cannot be transformed into an active cofactor. GTP cyclohydrolase I activity was not detectable in liver biopsies from the patient. The presence of an endogenous inhibitor in the patient's liver was excluded. This is the first case of a new variant of hyperphenylalaninemia in which the formation of dihydroneopterin triphosphate and its pterin metabolites in liver is markedly diminished. Normal activities of xanthine oxidase and sulfite oxidase were apparent since uric acid levels were normal and no increase in hypoxanthine, xanthine, and S-sulfocysteine concentrations could be observed in urine. It is concluded that the molybdenum cofactor of these enzymes may not be derived from dihydroneopterin triphosphate in man. Also, since no gross abnormalities in the patient's immune system could be found, it seems unlikely that dihydroneopterin triphosphate metabolites, such as neopterin, participate actively in immunological processes, as postulated by others. See Note added in proof.
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PMID:GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia. 673 69

L-Glutamic acid has been found to be a positive and L-lysine a negative modifier of the xanthine oxidase activity at the optimum pH (7.4) of the enzyme. Increase in pH was observed to be associated with a progressive decrease in the inhibition produced by L-lysine.
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PMID:Amino acids: modifiers of xanthine oxidase activity. 678 Apr 61

1. Human red blood cell membrane oxidase catalyzes the transformation of folic acid to pterin-6-aldehyde and p-aminobenzoyl glutamic acid provided hydrogen peroxide, a xanthine oxidase inhibitor, is present. Horseradish peroxidase produces the same product in the absence of hydrogen peroxide. 2. The oxidation of folic acid by horseradish peroxidase is accompanied by photon emission. Several lines of evidence suggest that singlet oxygen is the emitting species and is generated directly: a) the effects of singlet oxygen traps such as bilirubin, and of singlet oxygen enhancers such as 1,4-diazobicyclo 2.2.2 octane (DABCO) and eosin; b) the emission spectrum maximum of the unsensitized reaction was greater than 560 nm; c) enhancement of photon emission when the reaction was carried out in D2O, and d) no enhancement of the emission was observed when anthracenic energy acceptors were present. 3. Singlet oxygen production and the inactivation of xanthine oxidase may be important when considering folic acid metabolism by cancer cells, in view of the fact that the level of this enzyme is low in these cells.
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PMID:Human red blood cell membrane oxidase and horseradish peroxidase cleavage of folic acid: evidence for formation of singlet oxygen. 689 21

The use of NSAIDs (non-steroidal anti-inflammatory drugs), although of great therapeutic value clinically, is limited by their tendency to cause mucosal damage in the gastrointestinal tract. In the small intestine, the effects these drugs have been shown to produce include inhibition of cyclo-oxygenase, mitochondrial dysfunction and free radical-induced oxidative changes, all of which contribute to the mucosal damage seen. Glutamine is a fuel preferentially used by enterocytes and is known to contribute to maintaining the integrity of these cells. In the present study, we investigated the effect of glutamine on indomethacin-induced changes in the small intestinal mucosa. Rats were given 2% glutamine or glutamic acid or isonitrogenous amino acids, glycine or alanine, in the diet for 7 days. Indomethacin was then administered orally at a dose of 40 mg/kg of body weight. After 1 h, the small intestine was removed and used for the measurement of parameters of oxidative stress and mitochondrial and BBM (brush border membrane) function. Evidence of oxidative stress was found in the mucosa of the small intestine of drug-treated rats, as indicated by significantly increased activity of xanthine oxidase (P < 0.001) and myeloperoxidase (P < 0.001), with corresponding decreases in the levels of several free radical scavenging enzymes and alpha-tocopherol (P < 0.001 in all cases). Levels of products of peroxidation were also significantly elevated (P < 0.001 for all the parameters measured). In addition, oxidative stress was evident in isolated intestinal mitochondria and BBMs (P < 0.001 for all the parameters measured), with associated alterations in function of these organelles (P < 0.001 for all the parameters measured). Supplementation of the diet with glutamine or glutamic acid prior to treatment with indomethacin produced significant amelioration in all the effects produced by the drug in the small intestine (P < 0.001 for all the parameters measured). Glycine and alanine were found to be much less effective in these respects.
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PMID:Oral glutamine attenuates indomethacin-induced small intestinal damage. 1512 85

The oxidation process by molybdenum-containing enzyme, xanthine oxidase, is theoretically studied with a model complex representing the reaction center and a typical benchmark substrate, formamide. Comparisons were systematically made among reaction mechanisms proposed previously. In the concerted and stepwise mechanisms that were theoretically discussed previously, the oxidation reaction takes place with a moderate activation barrier. However, the product is less stable than the reactant complex, which indicates that these mechanisms are unlikely. Moreover, the product of the concerted mechanism is not consistent with the isotope experimental result. In addition to those mechanisms, another mechanism initiated by the deprotonation of the active site was newly investigated here. In the transition state of this reaction, the carbon atom of formamide interacts with the oxo ligand of the Mo center and the hydrogen atom is moving from the carbon atom to the thioxo ligand. This reaction takes place with a moderate activation barrier and considerably large exothermicity. Furthermore, the product by this mechanism is consistent with the isotope experimental result. Also, our computations clearly show that the deprotonation of the active site occurs with considerable exothermicity in the presence of glutamic acid and substrate. The intermediate of the stepwise mechanism could not be optimized in the case of the deprotonated active site. From all these results, it should be concluded that the one-step mechanism with the deprotonated active site is the most plausible.
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PMID:Oxidation reaction by xanthine oxidase: theoretical study of reaction mechanism. 1756 39