Molybdenum-Containing Flavoprotein Hydroxylases

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 

Xanthine oxidoreductase contains two molecules of molybdenum as molybdopterin (Section 10.5), two molecules of FAD, eight non-heme iron-sulfide groups, and two persulfide (—S—S—) groups. It exists as two interconvertible forms  

The xanthine dehydrogenase form catalyzes the oxidation of xanthine to hypoxanthine at the expense of NAD+. 

The xanthine oxidase form cannot utilize NAD+, but reduces oxygen to hydrogen peroxide. 

The dehydrogenase form of the enzyme is converted to the oxidase form by reversible oxidation of cysteine to form a disulfide bridge. The redox potential of the dehydrogenase form of the enzyme is considerably lower than that of the oxidase form, because the protein confers greater stability on the neutral flavin semiquinone radical (Rajagopalan and Johnson, 1992 Kiskeretal., 1997 Nishino and Okamoto, 2000). 

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Other enzymes may also be involved in the oxidation of aldehydes, particularly aldehyde oxidase and xanthine oxidase, which belong to the molybdenum hydroxylases. These enzymes are primarily cytosolic, although microsomal aldehyde oxidase activity has been detected. They are flavoproteins, containing FAD and also molybdenum, and the oxygen incorporated is derived from water rather than molecular oxygen. Aldehyde oxidase and xanthine oxidase in fact oxidize a wide variety of substrates, both aldehydes and nitrogen containing heterocycles such as caffeine and purines (see below). Aldehyde... 

Molybdenum hydroxylases (i.e., AO and XO) are flavoproteins that contain in addition to a FAD, a pterine cofactor coordinated to a molybdenum atom, and an iron sulfur center for their catalytic activity. They catalyze the two-electron oxidation of substrates with transfer to molecular oxygen to produce H2O2, and insert an atom of oxygen from water into a wide range of N-hctcrocycies and aldehydes via two-electron redox reaction as shown in equation 1.4 ... 

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