Xanthine oxidase distribution

Parks, D.A. and Granger, D.N. (1986). Xanthine oxidase biochemistry, distribution and physiology. Acta Physiol. Scand. 126 (Suppl. 548), 87-99. 

The distribution of trace elements among the compounds and physical phases in milk has not been elucidated completely. Molybdenum appears to be found exclusively in xanthine oxidase and Co in vitamin B12. Iron is an essential component of xanthine oxidase, lactoperoxi-dase, and catalase. About half of the total Fe and 10% of the Cu are in the fat globule membrane. Copper has been studied extensively in relation to oxidation of milk lipids. The trace metal present in highest con-... 

Disposition in the Body. Readily absorbed after oral administration bioavailability about 16%and very variable. It is distributed throughout the body water and diffuses into the cerebrospinal fluid. Mercaptopurine is activated in the body by intracellular conversion to nucleotide forms including the ribonucleotide thioinosinic acid. It is metabolised by xanthine oxidase to inactive 6-thiouric acid which is excreted in the urine inorganic sulphate may also be present. About 50% of an oral dose is excreted in the urine in 24 hours, up to 8% as unchanged drug. Small amounts are excreted for up to 17 days. 

Krenitsky, T.A. Tuttle, J.V. Cattan, E.L. and Wang, P. A comparison of the distribution and the electron acceptor specificities of xanthine oxidase and aldehyde oxidase. Comp Biochem Physiol 49B 687-703, 1974. 

There are probably more publications relating to xanthine oxidase than to any other enzyme studied, certainly more than those pertaining to aldehyde oxidase. This is presumably because the former enzyme is easily accessible from cow s milk rather than from animal tissue. It is not the purpose of this review to include all the data amassed on xanthine oxidase, as this has been fully covered in recent reviews [8, 12, 13]. Furthermore, most of our own work has been concerned with aldehyde oxidase. Thus, this report compares the properties of the molybdenum hydroxylases, where possible, in terms of distribution, substrate and inhibitor specificity and mechanism of oxidation. 

Table 3 2. COMPARATIVE DISTRIBUTION OF XANTHINE OXIDASE AND ALDEHYDE OXIDASE ACTIVITY IN MILK AND LIVER OF MAMMALIAN SPECIES [92, 93, 95]...

Aldehyde oxidase is structurally and chemically similar to xanthine oxidase, and both enzymes exhibit a similar distribution between tissues and share many common substrates, despite clear differences in certain catalytic properties. Thus, although both enzymes catalyze the oxidation of hypoxanthine to xanthine, conversion of the latter to uric acid is accomplished only by xanthine oxidase. 

Hypoxanthine, on the other hand, which accounts for only a fifth or so of the urinary uric acid is an active intermediate. It is degraded to xanthine and then to uric add by xanthine oxidase. This enzyme is found mainly in liver, kidney, and bowel, while guanase is widely distributed and would quickly deaminate any guanine formed. The product xanthine is a poor substrate for hypoxanthine phosphoribosyltrans-ferase (HPRT). Most of the hypoxanthine formed is reutiliiced by conversion to inosinic acid. Similar conclusions were reached by Ayvazian and Skupp in 1965 when they administered C-labeled purines to patients (A2). Furthermore, these studies and those earlier studies show that the xanthine is converted to hypoxanthine, presumably at the nucleotide level, and on the basis of what we know about microorganisms, we would assume it to be via guanine nucleotides (M2). Since label was found in urinary 7-methylguanine as early as 4 hours after administration of C-labeled purines, and since methylation of RNA occurs at the macromolecular level (B13), interconversion must be rapid and incorporation of some of these products into nucleic acids must also occur quickly. 

The assay method of xanthine oxidase from the duodenal mucosa using gastrofiberscopy is available for mass screening of this enzyme deficiency. The tissue distribution of this enzyme does not cause a problem in the liver. 

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