Purines xanthines

In many legumes, transportation of N from root to shoot occurs in the form of ureids, allantoin, and allantoic acid, which are synthesized from uric acid, an oxidation product of purine (xanthine). Poor growth of legumes in the presence of Mo deficiency can be ascribed in part to poor upward transport of N because of disturbed xanthine catabolism. In plants, oxidation of xanthine is mediated by another molybdoenzyme, xanthine dehydrogenase (Mendel and Muller, 1976 Nguyen and Feierabend, 1978). This enzyme has a constitution similar to that of the xanthine oxidase found in animals. It has two identical subunits, and each unit contains one Mo atom, one FAD, and four Fe-S groups. 

Allopurinol therapy in hyperuricaemic man has been shown to be advantageous from two points of view. Firstly, it reduces urinary uric acid excretion and increases the excretion of the precursor purines xanthine and, to a lesser extent, hypoxanthine. In addition, total urinary purine excretion (the sum of these three) may be reduced by as much as 0 during allopurinol therapy (1). This latter effect has been attributed to the formation of nucleotides of either hypoxanthine (1) or allopurinol itself (2), which in turn exert a feed back inhibitary effect on the first enzyme of de novo purine synthesis. 

The occurrence of the imidazole ring in both histidine and the purine bases has led to suggestions that there is a relationship between these metabohtes. The proposal that histidine might serve as a precursor of the purine bases has found no experimental support. Broquist and Snell observed that the combination of histidine and purine bases promoted the growth of L. arabinosus in the presence of pyridoxal (vitamin B ). In the absence of pyridoxal, histidine becomes essential and the purine bases are unable to supply it. From the higher requirement of guanine in the absence of histidine by L. casei and the decrease in the inhibitory effect of imidazolealdehyde on the growth of L. arabinosus in the presence of histidine, it was inferred that certain purines (xanthine) could serve as a precursor of histidine in the bacterial species mentioned above. 

Purines and pyrimidines are planar, aromatic, heterocyclic ring systems which absorb ultraviolet light. Formulas (V) and (VI) depict the two tautomeric forms of the purine xanthine which are in equilibrium with one another. Purines and pyrimidines exist predominantly in the keto form in aqueous solution (la). 

To end this chapter, we ll note that other kinds of complexes exist, whose formation may induce modifications of some physicochemical properties of the compounds giving them. Hence, their analysis may be perturbed. It is the case of ion pairs that we decided to include in the group of complexes and also of charge transfer derivatives. A good example is that of puric bases derived from 7H-purines xanthine, caffeine, theophylline, and theobromine. Some abnormal physical properties are exhibited by these derivatives. 

This enzyme, sometimes also called the Schardinger enzyme, occurs in milk. It is capable of " oxidising" acetaldehyde to acetic acid, and also the purine bases xanthine and hypoxanthine to uric acid. The former reaction is not a simple direct oxidation and is assumed to take place as follows. The enzyme activates the hydrated form of the aldehyde so that it readily parts w ith two hydrogen atoms in the presence of a suitable hydrogen acceptor such as methylene-blue the latter being reduced to the colourless leuco-compound. The oxidation of certain substrates will not take place in the absence of such a hydrogen acceptor. 

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

Adenine (6-amino purine) and guanine (2-amino-6-oxy purine), the two common purines, are found in both DNA and RNA (Figure 11.4). Other naturally occurring purine derivatives include hypoxanthlne, xanthine, and uric acid (Figure 11.5). Flypoxanthine and xanthine are found only rarely as constituents of nucleic acids. Uric acid, the most oxidized state for a purine derivative, is never found in nucleic acids. 

FIGURE 11.5 Other naturally occurring purine derivatives—hypoxanthine, xanthine, and uric acid. 

At the present time, the greatest importance of covalent hydration in biology seems to lie in the direction of understanding the action of enzymes. In this connection, the enzyme known as xanthine oxidase has been extensively investigated.This enzyme catalyzes the oxidation of aldehydes to acids, purines to hydroxypurines, and pteridines to hydroxypteridines. The only structural feature which these three substituents have in common is a secondary alcoholic group present in the covalently hydrated forms. Therefore it was logical to conceive of this group as the point of attack by the enzyme. 

Anti-gout Drugs. Figure 1 Xanthine oxidase-catalyzed reactions. Xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid, respectively. Hypoxanthine and xanthine are more soluble than uric acid. Xanthine oxidase also converts the uricostatic drug allopurinol to alloxanthine. Allopurinol and hypoxanthine are isomers that differ from each other in the substitution of positions 7 and 8 of the purine ring system. Although allopurinol is converted to alloxanthine by xanthine oxidase, allopurinol is also a xanthine oxidase inhibitor. Specifically, at low concentrations, allopurinol acts as a competitive inhibitor, and at high concentrations it acts as a noncompetitive inhibitor. Alloxanthine is a noncompetitive xanthine oxidase inhibitor. XOD xanthine oxidase. 

Schumacher HR Jr (2005) Febuxostat a non-purine, selective inhibitor of xanthine oxidase for the management of hyperaricaemia in patients with gout. Expert Opin Investig Drugs 14 893-903... 

Uric acid is the endproduct of purine metabolism in man. Uric acid has a lower solubility than its progenitor metabolites, hypoxanthine and xanthine. Impaired uric acid elimination and/or increased uric acid production result in hyperuricemia and increase the risk of gouty arthritis. At physiological pH, 99% of the uric acid molecules are actually in the form of the urate salt. A decrease in pH increases the fraction of uric acid molecules relative to urate molecules. Uric acid possesses lower solubility than urate. 

Xanthine oxidase (XOD) is the key enzyme in purine catabolism. XOD catalyses the conversion ofhypoxan-thine to xanthine and of xanthine to uric acid, respectively. The uricostatic drug allopurinol and its major metabolite alloxanthine (oxypurinol) inhibit xanthine oxidase. 

Purine derivatives (e. g. xanthine) are oxidized by chloramine T in the presence of hydrochloric acid and form purple-red anunonium salts of purpuric acid (murexide) with ammonia. Whether the murexide reaction is also the cause of the fluorescence is open to question. 

A series of annulated purines 114-6 have been synthesised as potential inhibitors of xanthine oxidase but, in general, they showed poor activity and the simple pyrimidines 117 were more effective in vitro < 96MI06 96CA(125)86586 96JMC2529 >. 

Because aromatic purines and purine nucleosides and free purines such as hypo-xanthine and guanine 242 are readily silylated-aminated [64] (cf Scheme 4.24), it is obvious that 6-membered hydroxy-N-heterocycles are analogously silylated-aminated, with reactivity in the order given in Scheme 4.25 [73] X=OTf is the best leaving group and X=NHSiMe3 (cf the transamination as discussed in Section 4.2.4) is the weakest. 

Figure 34-8. Formation of uric acid from purine nucleosides byway of the purine bases hypoxanthine, xanthine, and guanine. Purine deoxyribonucleosides are degraded by the same catabolic pathwayand enzymes,all of which existin the mucosa of the mammalian gastrointestinal tract.

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