Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen metabolites (ROMs) are partially reduced oxygen species that include superoxide, hydrogen peroxide, hydroxyl radical, and hypohalous acids. Formation of superoxide or hydrogen peroxide may be injurious to tissue directly; however, it is thought that the primary mediators of tissue damage are the secondarily derived oxidants such as hydroxyl radical and hypohalous acid. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of ROMs. Sources of ROMs in the gastrointestinal tract include mucosal oxidases such as xanthine oxidase, amine oxidase, and aldehyde oxidase as well as the NADPH oxidase found in the resident phagocytic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. We have demonstrated that reperfusion of ischemic small intestine results in substantial mucosal injury that is mediated by oxy radicals generated from xanthine oxidase and inflammatory leukocytes. The final mediator of toxicity appears to be the hydroxyl radical derived from the iron-catalyzed interaction between superoxide and hydrogen peroxide. Data from our laboratories as well as other laboratories suggest that reactive oxygen metabolites may play an important role in mediating mucosal injury during active episodes of ulcerative colitis. We present a working hypothesis which states that transient ischemic episodes in the bowel initiate a cascade of self-perpetuating cycles of ROM formation, inflammation and, ultimately, mucosal injury.
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PMID:Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites. 283 Oct 16

Aminoacetone (AA) is a threonine and glycine catabolite long known to accumulate in cri-du-chat and threoninemia syndromes and, more recently, implicated as a contributing source of methylglyoxal (MG) in diabetes mellitus. Oxidation of AA to MG, NH(4)(+), and H(2)O(2) has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by Cu(II) ions. We here study the mechanism of AA aerobic oxidation, in the presence and absence of iron ions, and coupled to iron release from ferritin. Aminoacetone (1-7 mM) autoxidizes in Chelex-treated phosphate buffer (pH 7.4) to yield stoichiometric amounts of MG and NH(4)(+). Superoxide radical was shown to propagate this reaction as indicated by strong inhibition of oxygen uptake by superoxide dismutase (SOD) (1-50 units/mL; up to 90%) or semicarbazide (0.5-5 mM; up to 80%) and by EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which detected the formation of the DMPO-(*)OH adduct as a decomposition product from the DMPO-O(2)(*)(-) adduct. Accordingly, oxygen uptake by AA is accelerated upon addition of xanthine/xanthine oxidase, a well-known enzymatic source of O(2)(*)(-) radicals. Under Fe(II)EDTA catalysis, SOD (<50 units/mL) had little effect on the oxygen uptake curve or on the EPR spectrum of AA/DMPO, which shows intense signals of the DMPO-(*)OH adduct and of a secondary carbon-centered DMPO adduct, attributable to the AA(*) enoyl radical. In the presence of iron, simultaneous (two) electron transfer from both Fe(II) and AA to O(2), leading directly to H(2)O(2) generation followed by the Fenton reaction is thought to take place. Aminoacetone was also found to induce dose-dependent Fe(II) release from horse spleen ferritin, putatively mediated by both O(2)(*)(-) and AA(*) enoyl radicals, and the co-oxidation of added hemoglobin and myoglobin, which may be viewed as the initial step for potential further iron release. It is thus tempting to propose that AA, accumulated in the blood and other tissues of diabetics, besides being metabolized by SSAO, may release iron and undergo spontaneous and iron-catalyzed oxidation with production of reactive H(2)O(2) and O(2)(*)(-), triggering pathological responses. It is noteworthy that noninsulin-dependent diabetes has been frequently associated with iron overload and oxidative stress.
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PMID:Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin. 1155 49