Enzyme xanthine oxidoreductase

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.)...

Successive, univalent reduction of oxygen may yield reactive oxygen species. This reduction can be effected photochemically, chemically or enzymatically (Korycka- Dahl and Richardson, 1980). A number of enzymes, including Xanthine oxidoreductase in milk, are capable of producing large amounts of superoxide via the univalent reduction of oxygen (Fridovich, 1976). 

The mechanism(s) by which Xanthine oxidoreductase exerts its prooxidant effect(s) is not fully understood. Hydrogen peroxide, resulting from oxidation of a suitable substrate by Xanthine oxidoreductase, could oxidize milk lipids. However, normal milk contains little or no substrate for the enzyme. A possible mechanism involving interaction between native and denatured Xanthine oxidoreductase in MFGM and lactoperoxidase or copper in milk serum has been proposed (Hill, 1979 Allen and Wreiden, 1982b). 

Xanthine oxidoreductase and aldehyde oxidase represent a distinct class of flavin-dependent oxidases. They both dehydrogenate andhydroxylate the substrate. However, unlike the mixed-function oxidases (Section 7.3.8), the oxygen introduced into the substrate by these enzymes is derived from water, and the role of molecular oxygen is in the reoxidation of the reduced flavin. Among other reactions, aldehyde oxidase is important in the oxidation of A( -methyl... 

The xanthine oxidoreductases are large, complex molybdo-flavoproteins with roles in the catabolism of purines, for example, oxidizing hypoxanthine to xanthine and xanthine to uric acid (equation 9). Xanthine oxidase can also catalyze the reduction of nitrate to nitrite (or in the presence superoxide, peroxynitrite) and the reduction of nitrite to nitric oxide. Peroxynitrite, a powerfiil and destructive oxidant, has been implicated in diseases such as arthritis, atherosclerosis, multiple sclerosis, and Alzheimer s and Parkinson s diseases. The microbicidal role of milk and intestinal xanthine oxidase may also involve the generation of peroxynitrite in the gut. The high levels of the enzyme in the mammary glands of pregnant... 

Uric acid (Fig. 1) in the human body is the end product of purine metabolism. It is produced by the enzymatic conversion of hypoxanthine to xanthine and then to uric acid. The enzyme involved here is xanthine oxidoreductase. This enzyme exists in two forms xanthine dehydrogenase and xanthine oxidase. The latter is able to produce oxidizing species during enzymatic catalysis [4]. In most organisms uric acid is enzymatically degraded by an enzyme called urate... 

Xanthine oxidoreductase and aldehyde oxidase are the principal enzymes involved in the oxidation of exocydic DNA adducts. Their role in purine catabolism and in the oxidation of nitrogen-rich heterocycles is well documented [143-145]. 

These enzymes (hydroxylases) are distributed across all phyla and include xanthine oxidoreductase (see Oxi-doreductase) (oxidase and dehydrogenase) aldehyde... 

Notable exceptions occur in the formate dehydrogenases and acetylene hydratase, and possibly in bacterial YedY " and the mitochondrial ami-doxime reducing component (mARC) enzyme. A markedly different type of reaction is catalyzed by members of the xanthine oxidoreductase (XOR) family of enzymes and involves the formal insertion of an oxygen atom into a substrate C-H bond. Thus, these enzymes are often categorized as hydroxylases.However, the reactivity patterns of the XORs differ substantially... 

The most intensively studied enzyme from this family is xanthine oxidoreductase, comprising the pairing of xanthine oxidase (XO) and xanthine dehydrogenase (XDH). These enzymes oxidize the heterocycles hypoxanthine... 

Xanthine dehydrogenase, XDH [E.C. 1.1.1.204], and the closely related isoenzyme xanthine oxidoreductase, XOR [E.C. 1.1.3.22], are molybdopterin oxidoreductive enzymes. The enzymes catalyze oxidation of a C-substrate atom by two electrons. In human body the enzymes convert the nucleic acid metabolite hypoxanthine into xanthine and xanthine into uric acid. Fig. 10.6 The reductive rate constant of XDH,... 

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