Xanthine properties

The effectiveness of theophylline in the treatment of asthma seems to result from a combination of biological properties which are not clearly understood (63). Detailed discussions of the possible role of xanthines in asthma may be found in references 64—66. 

It is possible that dietary flavonoids participate in the regulation of cellular function independent of their antioxidant properties. Other non-antioxidant direct effects reported include inhibition of prooxidant enzymes (xanthine oxidase, NAD(P)H oxidase, lipoxygenases), induction of antioxidant enzymes (superoxide dismutase, gluthathione peroxidase, glutathione S-transferase), and inhibition of redox-sensitive transcription factors. 

Studies bearing on the role of molybdenum in enzymes will be exemplified by a detailed summary of results on the most studied of these enzymes, which is undoubtedly milk xanthine oxidase. To put this in its context, it will be preceded by a review of the general properties of xanthine oxidase. The final section will then be a short account of work on some of the other molybdenum enzymes. 

A further controversy in the literature on xanthine oxidase preparations may be mentioned here. This concerns use of proteolytic enzymes in the purification procedure, a step first introduced by Ball (74), which undoubtedly increases yields of purified enzyme and generally simplifies the preparation. Despite suggestions to the contrary (70) it now seems (19, 58) that this treatment has little or no effect on the properties of the purified enzyme. 

It is of considerable interest, in attempting to understand catalysis by xanthine oxidase, to compare the properties of the active enzyme with those of the inactivated form. Radioactive tracer and other techniques have provided evidence (33) that (at least in its reduced form) the... 

In addition to xanthine oxidase, flavonoids are able to inhibit the activity of a wide range of enzymes. These inhibitory effects of flavonoids may depend both on their free radical scavenging and chelating properties. Thus, it has been shown that flavonoids inhibit... 

The absence of substituents with free radical scavenging properties in most of the (3-blockers makes doubtful their efficacy as powerful antioxidants. Arouma et al. [293] tested the antioxidative properties of several 3-blockers in reactions with superoxide, hydroxyl radicals, hydrogen peroxide, and hypochlorous acid. It was demonstrated that most of the compounds tested were inactive in these experiments. Nonetheless, propranolol, verapamil, and flunarizine effectively inhibited iron ascorbate-stimulated microsomal lipid peroxidation and all drugs (excluding flunarizine) were effective scavengers of hydroxyl radicals. Contrary to Janero et al. [292], these authors did not find the inhibition of xanthine oxidase by propranolol. It was concluded that 3-blockers are not the effective in vivo antioxidants. 

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... 

R is an electron-donor substrate such as purine or xanthine and A is an electron acceptor such as 02 or NAD+. It is thought that the in vivo mammalian form of xanthine oxidase uses NAD+ as acceptor and is therefore, more appropriately named xanthine dehydrogenase. No evidence exists for a dehydrogenase form of aldehyde oxidase. The specificities of xanthine oxidase and aldehyde oxidase have been extensively catalogued (96), and the mechanism and properties of these enzymes have been reviewed (97, 98). 

Upon purification of the XDH from C. purinolyticum, a separate Se-labeled peak appeared eluting from a DEAE sepharose column. This second peak also appeared to contain a flavin based on UV-visible spectrum. This peak did not use xanthine as a substrate for the reduction of artificial electron acceptors (2,6 dichlor-oindophenol, DCIP), and based on this altered specificity this fraction was further studied. Subsequent purification and analysis showed the enzyme complex consisted of four subunits, and contained molybdenum, iron selenium, and FAD. The most unique property of this enzyme lies in its substrate specificity. Purine, hypoxanthine (6-OH purine), and 2-OH purine were all found to serve as reductants in the presence of DCIP, yet xanthine was not a substrate at any concentration tested. The enzyme was named purine hydroxylase to differentiate it from similar enzymes that use xanthine as a substrate. To date, this is the only enzyme in the molybdenum hydroxylase family (including aldehyde oxidoreductases) that does not hydroxylate the 8-position of the purine ring. This unique substrate specificity, coupled with the studies of Andreesen on purine fermentation pathways, suggests that xanthine is the key intermediate that is broken down in a selenium-dependent purine fermentation pathway. ... 

Bradshaw WH, Barker HA. 1960. Purification and properties of xanthine dehydrogenase from Clostridium cylindrosporum. J Biol Chem 235 3620-9. 

Introduction.—A review discussing the properties of the molybdenum-containing enzymes, in particular the e.s.r. characteristics of xanthine oxidase, and a text describing the analytical chemistry of molybdenum and tungsten, have been published. 

Kim, Y.J. et al.. Superoxide anion scavenging and xanthine oxidase inhibition of (-l-)-catechin-aldehyde polycondensates. Amplification of the antioxidant property of (-l-)-catechin by polycondensation with aldehydes. Biomacromolecules, 5, 547, 2004. 

It undergoes marked self-association and can be purified readily by chromatography on porous glass. The enzyme has a molecular weight of about 89 kDa, a pH optimum of 6.8-7.0, and a temperature optimum of 35°C. Its amino acid composition, its requirement for iron but not for molybdenum and FAD, and the catalytic properties of the enzyme, indicate that sulphydryl oxidase is a distinct enzyme from xanthine oxidase and thiol oxidase (EC 1.8.3.2). 

Although the hypothesis of Egumi may be an oversimplification, it is certainly true that Fe /Feu is widely used in redox systems. Zn " in hydrolysis, esterification, and similar reactions, and molybdenum in nitrogenase. xanthine oxkkise. nitnite reductase, etc Putting abundance aside, discuss the specific chemical properties of these metals this make them well suited for their tasks. 

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