Xanthine dehydrogenase molybdenum

Koenig K, JR Andreesen (1990) Xanthine dehydrogenase and 2-furoyl-coenzyme A dehydrogenase from Pseudomonasputida Ful two molybdenum-containing dehydrogenases of novel structural composition. J Bacterial 172 5999-6009. 

Self WT (2002) Regulation of purine hydroxylase and xanthine dehydrogenase from Clostridium purinolyti-cum in response to purines, selenium and molybdenum. J Bacterial 184 2039-2044. 

Of the mammalian enzymes, the sulphite oxidase of bovine liver has only recently been discovered to contain molybdenum (15). The better known molybdenum enzymes, xanthine oxidase from cows milk (31) and aldehyde oxidase from rabbit liver (16) are closely related to one another as they are to the xanthine dehydrogenases from chicken liver (17) and from bacteria (18). 

Xanthine dehydrogenase from chicken liver reacts readily with NAD as acceptor (77) while that from Micrococcus lactilyticus is inactive towards this, reacting instead with ferredoxin (18). Both enzymes react only slowly with oxygen. It seems reasonable to assume, however, that for each member of this group of enzymes, reducing substrates all react via molybdenum, as in milk xanthine oxidase. Presumably, different... 

So little is known about molybdenum enzymes other than milk xanthine oxidase that there is little to be said by way of general conclusions. In all cases where there is direct evidence (except possibly for xanthine dehydrogenase from Micrococcus lactilyticus) it seems that molybdenum in the enzymes does have a redox function in catalysis. For the xanthine oxidases and dehydrogenases and for aldehyde oxidase, the metal is concerned in interaction of the enzymes with reducing substrates. However, for nitrate reductase it is apparently in interaction with the oxidizing substrate that the metal is involved. In nitrogenase the role of molybdenum is still quite uncertain. 

This enzyme [EC 1.1.3.22] catalyzes the reaction of xanthine with dioxygen and water to produce urate and hydrogen peroxide. Enzymatic activity requires iron, FAD, and molybdenum. Hypoxanthine and some other purines and pterins can act as substrates. Under some conditions, the product is mainly superoxide rather than hydrogen peroxide thus, R—H reacts with two dioxygen and water to produce R—OH, two H+, and two 02 molecules. The Micrococcus enzyme can use ferredoxin as the acceptor substrate. The mammalian enzyme can be interconverted to xanthine dehydrogenase [EC 1.1.1.204]. See Xanthine Dehydrogenase... 

METHOD OF CONTINUOUS VARIATION MOLYBDENUM COFACTOR (MoCo) Molybdenum-dependent reactions, ALDEHYDE OXIDASE MOLYBDOPTERIN NITRATE REDUCTASE NITROGENASE SULFITE OXIDASE XANTHINE DEHYDROGENASE MOLYBDOPTERIN... 

Rembold H (1983) Pteridine catabolism. In Curtius HC, Pfleidere W, Wachter H (eds) Biochemical and Clinical Aspects of Pteridines. Walter de Gruyter, Berlin, pp 107-122 Blau N, de Klerk JBC, Thony B, Heizmann CW, Kierat L, Smeitink JAM, Duran M (1996) Tetrahydrobiopterin loading test in xanthine dehydrogenase and molybdenum cofactor deficiencies. Biochem Mol Med 58 199-203... 

Coughlan, M. P. 1980. Aldehyde oxidase, xanthine oxidase and xanthine dehydrogenase. Hydroxylases containing molybdenum, iron-sulphur and flavin. In Molybdenum and Molybdenum-Containing Enzymes. M.P. Coughlan (Editor). Pergamon Press, Oxford, pp. 119-185. 

Fe prosthetic groups.282 283 A group of aldehyde oxidases and xanthine dehydrogenases also contain molybdenum as well as iron (Chapter 16). In every case the metal ions are bound independently of the flavin.2833... 

Long recognized as an essential element for the growth of plants, molybdenum has never been directly demonstrated as a necessary animal nutrient. Nevertheless, it is found in several enzymes of the human body, as well as in 30 or more additional enzymes of bacteria and plants.632 Aldehyde oxidases,633 xanthine oxidase of liver and the related xanthine dehydrogenase, catalyze the reactions of Eqs. 16-58 and 16-59 and contain molybdenum that is essential for catalytic activity. Xanthine oxidase also contains two Fe2S2 clusters and bound FAD. The enzymes can also... 

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... 

Cyanolyzed xanthine oxidase and xanthine dehydrogenase are inactive for the oxidation of xanthine to uric acid [159]. Cyanide abstracts a sulfur atom from the cofactor generating MoIV Upon reoxidation a bis(oxido) molybdenum (VI) with an average Mo=0 bond distance of 1.67 A is generated (Eq. 5). Upon reduction of cyanolyzed xanthine oxidase with dithionite one oxido ligand is... 

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