Xanthine oxidase coenzyme

The rationale for studies on flavin semiquinone metal interactions stems from the presence of flavin coenzymes which participate in electron transfer in a number of metalloflavoproteins. Iron-containing redox centers such as the heme and nonheme iron sulfur prosthetic groups (Fe2/S2, Fe+ZS, or the rubredoxin-type of iron center) constitute the more common type of metal donor-acceptor found in metalloflavoproteins, although molybdenum is encountered in the molybdenum hydroxylases (e.g. xanthine oxidase, aldehyde dehydrogenase). 

Figure 16-31 (A) Structure of molybdopterin cytosine dinucleotide complexed with an atom of molybdenum. (B) Stereoscopic ribbon drawing of the structure of one subunit of the xanthine oxidase-related aldehyde oxidoreductase from Desulfo-vibrio gigas. Each 907-residue subunit of the homodimeric protein contains two Fe2S2 clusters visible at the top and the molybdenum-molybdopterin coenzyme buried in the center. (C) Alpha-carbon plot of portions of the protein surrounding the molybdenum-molybdopterin cytosine dinucleotide and (at the top) the two plant-ferredoxin-like Fe2S2 clusters. Each of these is held by a separate structural domain of the protein. Two additional domains bind the molybdopterin coenzyme and there is also an intermediate connecting domain. In xanthine oxidase the latter presumably has the FAD binding site which is lacking in the D. gigas enzyme. From Romao et al.633 Courtesy of R. Huber.

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... 

The bioconversion of alcohols to aldehydes and ketones is catalyzed by soluble alcohol dehydrogenases present in the liver and other tissues. NAD is required os a coenzyme, although NADP also may serve as a coenzyme. The reaction catalyzed by alcohol dehydrogenase is reversible but often proceeds to the right because the aldehyde formed is fuithcr oxidized to the acid. Several aldehyde dehydrogenases, including aldehyde oxidase and xanthine oxidase, carry out the oxidation of aldehydes to their corresponding acids." - ... 

It is the coenzyme of xanthine oxidase, aldehyde oxidase and other aerobic dehydrogenases. Like riboflavin and FMN, FAD is universally present in the biosphere. It is reddish-yellow in colour but, like FMN and riboflavin, its solutions are a yellow-green. 

Another important naturally occurring pteridine is molybdopterin, apparently (9.28), which is the coenzyme of xanthine dehydrogenase, aldehyde oxidase, nitrate reductase, sulphite oxidase and presumably other enzymes that need both molybdenum and iron to function (Johnson and Rajagopolan, 1982). Xanthopterin, a co-lymphokine (p. 182), inhibits proliferation of lymphocytes (Ziegler 1983). 

---