Xanthine dehydrogenase properties

Saito, T., Nishino, T., Differences in redox and kinetic properties between NAD-dependent and 02-dependent types of rat liver xanthine dehydrogenase. J. Biol. Chem. 264 (1989), p. 10015-10022... 

R is an electron-donor substrate such as purine or xanthine and A is an electron acceptor such as 02 or NAD+. It is thought that the in vivo mammalian form of xanthine oxidase uses NAD+ as acceptor and is therefore, more appropriately named xanthine dehydrogenase. No evidence exists for a dehydrogenase form of aldehyde oxidase. The specificities of xanthine oxidase and aldehyde oxidase have been extensively catalogued (96), and the mechanism and properties of these enzymes have been reviewed (97, 98). 

Bradshaw WH, Barker HA. 1960. Purification and properties of xanthine dehydrogenase from Clostridium cylindrosporum. J Biol Chem 235 3620-9. 

These enzymes catalyze the two-electron oxidation of purines, aldehydes and pyrimidines, sulfite, formate and nicotinic acid in the general reaction shown in equation (49). These enzymes show some differences in properties. Xanthine oxidase, xanthine dehydrogenase and aldehyde oxidase all have relatively low redox potentials and a unique cyanolyzable sulfur atom, and so will be discussed together. 

Nguyen, J., and Feierabend, J. (1978). Some properties and subcellular localization of xanthine dehydrogenase in pea leaves. Plant Sci. Lett. 13 125-32. 

XOR accelerates the hydroxylation of purines, pyrimidines, pterins and aldehydes [132]. In humans, the enzyme catalyzes the last two steps of purine catabolism the oxidation of hypoxanthine to xanthine and of the latter to uric acid. An unusual property of this, but not aU XOR enzymes [133], is its interconversion between xanthine dehydrogenase and xanthine oxidase activities which implies a switch between NAD" and molecular oxygen being used as the final electron acceptor [134]. Structural studies suggest that this switch, that can be irreversibly induced by proteolysis [135], results from conformational changes that lead to both restricted access to the NAD cofactor to its binding site and changes in the redox potential of the FAD cofactor [136],... 

Battelli, M. G., Lorenzoni, E. and Stirpe, F. 1973. Milk xanthine oxidase type D (dehydrogenase) and type 0 (oxidase). Purification, interconversion and some properties. Biochem. J. 131, 191-198. 

Xanthine hydrogenase and aldehyde dehydrogenase also give desulfo proteins which have no catalytic activity and lower redox potentials. A molybdenum protein from Desulfovibrio gigas has been isolated, which appears to have similar properties to the desulfo proteins.1011... 

Purified xanthine oxidase reacts rapidly with oxygen, but it is now widely accepted that native enzyme exists mainly as a dehydrogenase, with NAD + as its natural acceptor [35-37]. This form, originally termed Type D by Della Corte and Stirpe [38], constitutes at least 80% of hepatic, intestinal or milk xanthine oxidase activity [37-40]. Studies on the properties of the Type D enzyme are complicated by the facile conversion of this form to at least two oxidases (Type O), depending on the method used, (i) Treatment with proteolytic enzymes causes an irreversible conversion of Type D to Type O [35]. Waud and Rajagopalan have proposed that this is due to the cleavage of... 

Metallo-Flavoproteins. As was mentioned in the case of cytochrome reductase, enzymes are known that contain metal cofactors in addition to flavin. These are called metallo-flavoproteins. The presence of metals introduces complexity into the reaction, since the metals involved, iron, molybdenum, copper, and manganese, all exist in at least two valence states and can participate in oxidation-reduction reactions. The enzymes known to be metallo-flavoproteins include xanthine oxidase, aldehyde oxidase, nitrate reductase, succinic dehydrogenase, fatty acyl CoA dehydrogenases, hydrogenase, and cytochrome reductases. Before these are discussed in detail some physical properties of flavin will be presented. 

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