Xanthine oxidoreductase

In contrast to inorganic nitrate [88] or nitrite [85], which are reduced at the Mo site of XOR, organic nitrates were shown [81] to be reduced initially at the FAD site of XOR (Fig. 2.4). As discussed above, cytochrome P-450 can catalyse the same reduction and other flavoproteins, as yet unidentified, may well do the same. Indeed organic nitrates have been shown to be reduced by flavins alone [89]. 

Although generation of NO, catalysed by purified XOR in the presence of GTN, is relatively slow [81], O Byrne et al. [90] were able to demonstrate NO-induced inhibition of platelet aggregation, in platelet-rich human plasma, in the presence of GTN and XOR. The anti-aggregation effect was dose-deperidenlly inhibited by 

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Free Radical-Mediated Biological Activity of Xanthine Oxidoreductase... 

Two forms of xanthine oxidoreductase namely XO and XDH are present in many human and animal cells and plasma, XDH and XO are the predominant species in cytoplasma and serum, respectively [39]. Damaging effects of XO-catalyzed superoxide production in post-ischemic tissues were demonstrated by many authors. For example, Chambers et al. [40] and Hearse et al. [41] have shown that the suppression of superoxide production by the administration of XO inhibitor allopurinol or SOD resulted in the reduction of infarct size in the dog and of the incidence of reperfusion-induced arrhythmia in the rat. Similarly, Charlat et al. [42] has also shown that allopurinol improved the recovery of the contractile function of reperfused myocardium in the dog. However, the use of allopurinol as the XO inhibitor has been questioned because this compound may affect oxygen radical formation not only as a XO inhibitor but as well as free radical scavenger [43]. Smith et al. [44] also showed that gastric mucosal injury depends on the oxygen radical production catalyzed by XO and iron. 

Harrison, R., Structure and function of xanthine oxidoreductase where are we now Free Radical Biol. Med. 33 (2002), p. 774-797... 

Millar, T. M., Stevens, C. R., Benjamin, N., Eisenthal, R., Harrison, R., Blake, D. R., Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions. FEBS Lett. 427 (1998), p. 225-228... 

Sanders, S. A., Eisenthal, R., Harrison, R., NADH oxidase activity of human xanthine oxidoreductase Generation of superoxide anion. 

Nitrite can be reduced in vivo to NO by oxyhemeoglobin [9], At the same time organic nitrites are substrates for xanthine oxidoreductase and direct reduction to NO occurs under anaerobic conditions [8],... 

Xanthine oxidoreductase (XOR) is a molybdenum-containing complex homodimeric 300-kDa cytosolic enzyme. Each subunit contains a molybdopterin cofactor, two nonidentical iron-sulfur centers, and FAD (89). The enzyme has an important physiologic role in the oxidative metabolism of purines, e.g., it catalyzes the sequence of reactions that convert hypoxanthine to xanthine then to uric acid (Fig. 4.36). 

Figure 17.3 The active site structure of xanthine oxidoreductase and the structure of the bovine enzyme with the two Fe-S domains (green and blue), the FAD domain (grey) and the molybdenumbinding domain (red). (From Hille, 2005. Copyright 2005, with permission from Elsevier.)...

Massey V, Harris CM. 1997. Milk xanthine oxidoreductase the first one hundred... 

Milk fat is present in spherical droplets, which range from about 0.2 to 15.0 pm in diameter, with the bulk of the fat being in globules 1.0 to 8.0 pm diameter. The MFGM, which envelopes the fat globule, consists largely of proteins and lipids. The protein of the membrane has a complex composition and over 40 polypeptides have been identified. Xanthine oxidoreductase,... 

Bruder, G., Heid, H.W., Jarasch, E.-D., Keenan, T.W., Mather, I.H. 1982. Characteristics of membrane-bound and soluble forms of Xanthine oxidoreductase from milk and endothelial cells of capillaries. Biochim. Biophys. Acta 701, 357-369. 

McManaman, J.L., Palmer, C.A., Wright, R.M., Neville, M.C. 2002. Functional regulation of Xanthine oxidoreductase expression and localization in the mouse mammary gland evidence of a role in lipid secretion. J. Physiol. 545.2, 567-579. 

Mondy, B.L., Keenan, T.W. 1993. Butyrophilin and Xanthine oxidoreductase occur in constant molar proportions in milk lipid globule membrane but vary in amount with breed and stage of lactation. Protoplasma. 177, 32-36. 

Spitsberg, V.L., Gorewit, R.C. 1998. Solubilization and purification of Xanthine oxidoreductase from bovine milk fat globule membrane. Protein Expression Purif. 13, 229-234. 

Valivullah, H.M., Keenan, T.W. 1989. Butyrophilin of milk lipid globule membrane contains N-linked carbohydrates and cross-links with Xanthine oxidoreductase. Int. J. Biochem. 21, 103-107. 

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