Liver xanthine dehydrogenase

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... 

Desulfo enzymes can be regenerated by anaerobic treatment with sulfide plus dithionite. Cyanide-inactivated turkey liver xanthine dehydrogenase is also reactivated by selenide, suggesting that selenium may replace sulfur in the active centre. 

DlArdenne, S. C., and Edmondson, D. E., 1990, Kinetic isotope effect studies on milk xanthine oxidase and on chicken liver xanthine dehydrogenase. Biochemistry 29 904611 9052. 

Nishino, T., and Nishino, T., 1987, Evidence for a tyrosine residue in the nicotinamide adenine dinucleotide binding site of chicken liver xanthine dehydrogenase. Biochemistry 26 3068n3072. 

Epstein, A., and Newburgh, R. W., 1972-1973, Synthesis and degradation of chicken liver xanthine dehydrogenase during development, Mech. Ageing and Dev. 1 431. 

Stirpe, F. and Della Corte, E. (1969). The regulation of rat liver xanthine oxidase. Conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O). J. Biol.Chem. 244, 3855-3863. 

Marubayashi, S., Kiyohiko, D., Yamada, K. and Kawasaki, T. (1991). Role of conversion of xanthine dehydrogenase to oxidase in ischaemic tat liver cell injury. Surgery 110, 537-543. 

McKelvey, T.G., Hollwarth, M.E., Granger, D.N., Engerson, T.D., Landler, U. and Jones H.P. (1988). Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischaemic rat liver and kidney. Am. J. Physiol. 254, G753-G760. 

Xanthine dehydrogenase Chicken liver Purines, aldehydes NAD... 

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... 

In man, BH4 is degraded either nonenzymatically by side-chain cleavage to pterin or is enzymatically metabolized in the gastrointestinal tract to become a lumazine [2]. Pterin and dihydropterin are converted by xanthine dehydrogenase to isoxanthopterin and xanthopterin, respectively [3,4]. It is assumed, however, that most of the ingested BH4 is used as a cofactor (mainly for PAH in the liver) and is catabolized to nonfluorescing compounds it may even be degraded to C02 and ammonia. 

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... 

Figure 2.3(D). Uricogenesis during alanine catabolism and gluconeogenesis in avian liver. Some abbreviations are as in figure 2.3(C). 1 C refers to one-carbon units MDH, malate dehydrogenase XDH, xanthine dehydrogenase PRPP, phosphoribosylpyrophosphate IMP, inosoine monophosphate ino, inosine hyp, hypoxanthine xan, xanthine.

In addition to liver aldehyde dehydrogenase, a number of other enzymes present in the soluble fraction of liver homogenates will oxidize aldehydes and certain N-heterocyclic compounds. Among these are aldehyde oxidase and xanthine oxidase (see below), both flavoprotein enzymes containing molybdenum. These enzymes catalyze the oxidation of aldehydes formed by the deamination of endogenous amines by amine oxidases. 

The cytosolic enzyme xanthine dehydrogenase catalyses the oxidation of hypoxanthine and xanthine to uric acid. It is thought to be located predominantly in the liver, small intestine and capillary endothelium in man [9]. However, the distribution is different in other species. In healthy tissue, most of the enzyme is present as the D form , which transfers electrons to NAD+ ... 

Guanine nucleotides follows a similar pathway where the amino group is oxidized to a keto group and there is removal of phosphate and then ribose to form xanthine. Thus, the two products of purine metabolism are hypoxanthine and xanthine. These are water soluble and can exit the cell and be carried to the liver for further oxidation. An enzyme called xanthine dehydrogenase (which contains molybidium) can oxidize hypoxanthine to xanthine and xanthine to uric acid. 

Some oxidations are mediated by hepatic enzymes localized outside the microsomal system. Alcohol dehydrogenase and aldehyde dehydrogenase, which catalyse a variety of alcohols and aldehydes such as ethanol and acetaldehyde, are found in the soluble fraction of the liver. Xanthine oxidase, a cytosolic enzyme mainly found in the liver and in small intestine, but also present in kidneys, spleen and heart, oxidizes mercaptopurine to 6-thiouric acid. Monoamine oxidase, a mitochondrial enzyme found in liver, kidney, intestine and nervous tissue, oxidatively deanoinates several naturally occurring amines (catecholamines, serotonin), as well as a number of drugs. 

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