Xanthine oxidation

Allopurinol markedly reduces xanthine oxide catabolism of the purine analogs, potentially increasing active 6-thioguanine nucleotides that may lead to severe leukopenia. The dose of 6-MP or azathioprine should be reduced by at least half in patients taking allopurinol. 

Prusiner. P. and M. Sundaralingam. 1972. Stereochemistry of nucleic acids and their constituents XXIX. Crystal and molecular structure of allopurinol, a potent inhibitor of xanthine oxid ste Cryst. 

Lipmann, F., Owen, C.R. 1943. The antibacterial effect of enzymatic xanthine oxidation. 

Table I also shows the great diversity of organisms in which iron—sulfur proteins have been detected. Thus far there is no organism which when appropriately examined has not contained an iron-sulfur protein, either in the soluble or membrane-bound form. Iron-sulfur proteins catalyze reactions of physiological importance in obligate anaerobic bacteria, such as hydrogen uptake and evolution, ATP formation, pyruvate metabolism, nitrogen fixation, and photosynthetic electron transport. These properties and reactions can be considered primitive and thus make iron-sulfur proteins a good place to start the study of evolution. These key reactions are also important in higher organisms. Other reactions catalyzed by iron-sulfur proteins can be added such as hydroxylation, nitrate and nitrite reduction, sulfite reduction, NADH oxidation, xanthine oxidation, and many other reactions (Table II).

SOD activity was assessed using a Ransod kit (Randox Laboratories Ltd.) that quenches the rate of inhibition of 2-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyltetrazolium (INT) reduction by the superoxide anion released after xanthine oxidation with xanthine oxidase. One unit of SOD causes a 50% inhibition rate and the activity was expressed as U mL of whole blood and reported to the normal range. In each case, appropriate control serum for quality control had been used. 

In the case of xanthine oxidation by XnO/XnDH (Scheme 7.1), oxidized enzyme (1) is reduced to a hydrosulfido-Mo(iv) centre, [(MPT)Mo" 0(SH) (urate)] " (5), upon substrate oxidation. This is then oxidized by one electron to produce the very rapid Mo(v) form, [(MPT)Mo OS(urate)] (6), named after the very rapid [fi2 10 ms) appearance of the attendant very rapid EPR signal. Displacement of oxidized substrate by hydroxide and further oxidation releases uric acid and regenerates the oxidized enzyme. Many other Mo(v) states can be generated during the turnover or inhibition of Mo hydroxylases. Various one-electron reduced Mo Cu forms of CODH have... 

The crystal structure of the four distinct redox cofactors of bovine milk XO is shown in Figure 5.2 as a representative example of XO and XDH. The Mo active site, two 2Fe-2S clusters (FeSI and FeSII) and FAD are apparent and electrons flow from Mo" to FAD (left to right) after (hypo)xanthine oxidation (hydroxylation) and NAD binds at the FAD site to be reduced by FAD. Of the XO/XDH enzymes to be studied to date the Mo " and Mo " redox potentials are consistently low amongst the lowest of all Mo enzymes (-350 mV to -500 mV vs. NHE). The two FAD redox potentials (FADVFADH and FADH/ FADH2) fall in the range (-250 to -400 mV vs. NHE). 

This profile was also obtained upon analysis of the ASC + Cu" " " + H2O2 and xanthine/xanthine oxidase/zymosan/bicarbonate CL systems. However, xanthine oxidation of acetaldehyde in the presence of bicarbonate resulted in peak intensity at about 435 my a value previously reported l y Henry (1977). 

Lucigenin enhances the rate of cytochrome c reduction with xanthine as substrate, but does not increase the rate of xanthine oxidation (Afanas ev et al. 1999). When NADH is used as a substrate, lucigenin inhibits the SOD-dependent components of cytochrome c reduction and enhances both the SOD-independent cytochrome c reduction and NADH oxidation, being a sole acceptor of an electron from the enzyme. 

PULSE RADIOLYSIS STUDY OF HYPOXANTHINE AND XANTHINE OXIDATION... 

Xanthine oxidation (Figure 4.10) for diagnostic purposes can easily be realized in any reaction device. In an MER, however, test sensitivity has been reported to exceed classical variants without, however, quantitative information being available [23]. 

With every mammalian extract studied, the xanthine-oxidizing activities with oxygen and with NAD as electron acceptors were additive. The sum of these separately measured activities closely approximated the rate of urate formation when both acceptors were present simultaneously. This additivity indicated that NAD did not compete with oxygen as an electron acceptor. 

The molecular properties of XDH fi om soybean nodules were investigated by Triplett et al. (1982). The enzyme was purified to homogeneity and found to be a molybdoflavoprotein with two subunits of 141,000 containing two molybdenum and eight iron atoms per molecule. The enzyme contained flavin mononucleotide (FMN) as the flavin cofactor, in contrast with other xanthine-oxidizing enzymes, which contain flavin adenine dinucleotide (FAD). 

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