Xanthine oxidase activity

Reperfusion of the synovial membrane occurs when exercise is stopped and O2 is subsequently reintroduced to the tissue. O2 is a substrate required for xanthine oxidase activity and O2" is generated. Therefore, repeated cycles of rest-exercise-rest in the inflamed joint may provide a continuous flux of destructive ROM. 

Pence, B.C. and Reiners, J.J. (1987). Murine epidermal xanthine oxidase activity correlation with degree of hyperplasia induced by tumor promoters. Cancer Res. 47, 6388-6392. 

Phon, S.H., Gannon, D.E., Varan, J., Ryan, V.S. and Ward, P.A. (1989). Xanthine oxidase activity in rat pulmonary artery endothelial cells and its alteration by activated neutrophils. Am. J. Path. 134, 1201-1211. 

Pitt, R.M., McKelvey, T.G., Saenger, J.S., Shah, A.K., Jones, H.P., Manci, E.A. and Powell, R.W. (1991). A tungsten-supplemented diet delivered by transplacental and breastfeeding routes lowers intestinal xanthine oxidase activity and affords cytoprotection in ischaemia-reperfusion injury to the small intestine. J. Paediatr. Suig. 26, 930-935. 

Numerous studies were dedicated to the effects of flavonoids on microsomal and mitochondrial lipid peroxidation. Kaempferol, quercetin, 7,8-dihydroxyflavone and D-catechin inhibited lipid peroxidation of light mitochondrial fraction from the rat liver initiated by the xanthine oxidase system [126]. Catechin, rutin, and naringin inhibited microsomal lipid peroxidation, xanthine oxidase activity, and DNA cleavage [127]. Myricetin inhibited ferric nitrilotriacetate-induced DNA oxidation and lipid peroxidation in primary rat hepatocyte cultures and activated DNA repair process [128]. 

Later on, the importance of xanthine oxidase as the producer of reoxygenation injury was questioned at least in the cells with low or no xanthine oxidase activity. Thus, it has been shown that human and rabbit hearts, which possess extremely low xanthine oxidase activity, nonetheless, develop myocardial infractions and ischemia-reperfusion injury [9], However, recent studies supported the importance of the xanthine oxidase-catalyzed oxygen radical generation. It has been showed that xanthine oxidase is partly responsible for reoxygenation injury in bovine pulmonary artery endothelial cells [10], human umbilical vein and lymphoblastic leukemia cells [11], and cerebral endothelial cells [12], Zwang et al. [11] concluded that xanthine dehydrogenase may catalyze superoxide formation without conversion to xanthine oxidase using NADH instead of xanthine as a substrate. 

Increase in blood and urine Mo levels, increases in serum ceruloplasmin, increased xanthine oxidase activity (11) Increased uric acid, decreased copper excretion, high incidence of gout-like disease (11)... 

Rajan, T. S., Richardson, G. A. and Stein, R. W. 1962. Xanthine oxidase activity of milks in relation to stage of lactation, feed, and incidence of spontaneous oxidation. J. Dairy Sci. 45, 933-934. 

Cerbulis, J. and Farrell, H. M. 1977. Xanthine oxidase activity in dairy products. J. Dairy Sci. 60, 170-176. 

Clark, A. J. and Pratt, D. E. 1976. Xanthine oxidase activity in rat serum after administration of homogenized bovine cream preparation. Life Sci. 19, 887-892. 

McCarthy, R. D. and Long, C. A. 1976. Bovine milk intake and xanthine oxidase activity in blood serum. J. Dairy Sci. 59, 1059-1062. 

While bovine milk is a rich source of xanthine oxidase, milks from some species do not necessarily contain appreciable amounts of enzymatically active xanthine oxidase. For example, human milk contains only traces of xanthine oxidase activity as measured by oxidation of xanthine or hypoxanthine (Zikakis and Treece 1971 Zikakis et aL 1976), yet a band corresponding in electrophoretic mobility to xanthine oxidase is a major constituent of human milk lipid globule membrane (Freudenstein et al. 1979 Murray et cd. 1979). Evidence that the membrane-bound form of xanthine oxidase in bovine lipid globule membrane contains small amounts of tightly bound fatty acid has been obtained (Keenan et al. 1982). Whether this property promotes attraction between the membrane or membrane-associated coat and the surface of the globule core remains to be determined. 

The first hint of an essential role of molybdenum in metabolism came from the discovery that animals raised on a diet deficient in molybdenum had decreased liver xanthine oxidase activity. There is no evidence that xanthine oxidase is essential for all life, but a human genetic deficiency of sulfite oxidase or of its molybdopterin coenzyme can be lethal.646,646a,b The conversion of molybdate into the molybdopterin cofactor in E. coli depends upon at least five genes.677 In Drosophila the addition of the cyanolyzable sulfur (Eq. 16-64) is the final step in formation of xanthine dehydrogenase.678 It is of interest that sulfur (S°) can be transferred from rhodanese (see Eq. 24-45), or from a related mercaptopyruvate sulfurtransferase679 into the desulfo form of xanthine oxidase to generate an active enzyme.680... 

Kalow W, Tang BK. Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 1991 50 508-519. 

Tai LA, Hwang KC. Control of xanthine oxidase activity by light. Angew Chem Int Ed 2000 39 3886-8. 

Figure 5. Proposed coupled proton-electron transfer scheme for xanthine oxidase activity (66, 67, 68)...

Many experimental observations on xanthine oxidase activity are correlated by this scheme, and at present, there appear to be no major inconsistencies. The coupled proton-electron transfer scheme (66, 67, 68) has been successfully incorporated into an overall mechanistic scheme (69) which explains, with great economy, a large amount of rather demanding data, from both kinetic and electron uptake experiments. 

Kashuba ADM, Bertino JS, Kearns GL et al. (1998) Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping. Clin Pharmacol Ther 63 540-551... 

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