Uric acid Constitution

Uric acid (2,6,8-hydroxypurine) is formed in small amounts in man, and traces are found in blood, urine, and feces. In birds and reptiles uric acid constitutes the normal metabolic end product of nitrogen and is found in large amounts in guano. 

Onanism, melancholy, and gout, unfortunately, were but way-stations on the road to final catastrophe. The uric acid deposits in a person s tissues would gradually increase in quantity as the years passed and as his constitutional vigor waned, until at last, Haig predicted, "the long pent up store of urates breaks its dams and rushes into the circulation with an overwhelming flood." If not destroyed on the rocks of apoplexy, the helpless victim would be swept onward to heart failure, Bright s disease, or a like fate. (25)... 

Oxidation of xanthine or uric acid derivatives with chromic acid gives the appropriate alloxane and urea as primary products which undergo further oxidation to corresponding parabanic acids (imidazolidine-2,4,5-triones) and purpuric acids which, on addition of ammonia, constitute the murexide test. This is positive for all purines capable of oxidation to an alloxane derivative, For a review see ref 48. 

Cyanuric Acid.—That iso-cyanic acid has the constitution given to it is established by the constitution of the alkyl derivatives which are not true esters (p. 73) and also by its relation to cyanuric acid. This latter acid is a polymer of iso-cyanic acid, viz., (HNCO)3. It is obtained by heating urea and the reactions will be considered presently when we study this compound. This source of the acid is the basis of the name cyan-uric acid. It is a solid crystallizing from water solution in prisms which contain two molecules of water of crystallization. Like iso-cyanic acid cyanuric acid yields alkyl derivatives of two isomeric forms, corresponding to polymers of cyanic and iso-cyanic acid derivatives. The ethyl derivatives have the following constitutions ... 

Constitution.— The constitution of uric acid has been established by a remarkable set of syntheses based upon a study of the products of decomposition. In this work several men played an important part. The most comprehensive work which cleared up the question of the constitution not only of uric acid but of several related compounds, which we shall presently consider, was by Emil Fischer, whom we have already mentioned in connection with two other groups of compounds intimately connected with plants and animals, viz., the carbohydrates and the proteins (p. 393). Earlier important work was done by Liebig and Wohler, and the relationship of the decomposition products was mainly due to the work of Baeyer. The accepted formula was first suggested by Medicus, and the syntheses supporting it were worked out by Horbaczewski, and by Behrend and Roosen. 

From the facts that uric acid yields the di-ureid allantoin and also equal molecules of alloxan, a mono-ureid, and urea it was concluded that uric acid must contain two urea residues. From the constitution of alloxan and its reduction products, barbituric and dialuric acids, uric acid must likewise contain a three carbon chain linked to a urea residue by the end carbon atoms. Also, as it yields parabanic acid or oxalyl urea, one of the urea residues must be linked to two adjacent carbon atoms in this chain. 

The splitting of the compound at the dotted line would yield alloxan and urea while splitting at the broken line would yield parabanic acid and urea. Confirmation of this constitution has been furnished in two ways (i) by Fischer s study of the methyl substitution products of uric acid and (2) by the syntheses of Horbaczewski and of Behrend and Roosen. 

From his work on uric acid Fischer was led to study these bases. He showed that they are directly related to uric acid and the proof of their constitution cleared up the whole question in regard to uric acid. It will be unnecessary here to go into detail in regard to the various syntheses and reactions by which this relationship was established. Suffice it to give the conclusions. 

Fischer.— Later Emil and OttO Fischer, the former being the one to whom we have repeatedly referred in connection with uric acid, carbohydrates and proteins, proved that the constitution of para-rosaniline was as we have previously given it and developed the methods of synthesis. 

The purine group of alkaloids includes the vegetable alkaloids caffeine, theobromine, theophylline and the animal alkaloids xanthine, hypoxanthine, guanine and adenine. The most common substance which is a purine compound is uric acid, but, though directly related to the alkaloids given above, it is not itself usually considered as an alkaloid. The constitution of uric acid has been fully considered (Part I, p. 442). It is the tri-hydroxy derivative of a substance known as purine which is the mother substance of the purine alkaloids also. 

As shown in the above formulas uric acid exists in tautomeric forms, having the constitution either of a hydroxyl compound, enol form, or of a ketone, keto form. The purine alkaloids which we have mentioned are similar hydroxyl or amino derivatives of purine. As tautomeric compounds they also exist in the two forms. Those which contain hydroxyl groups have the enol and the keto forms, while, if they contain ammonia residues instead of hydroxyl, they have the corresponding amino or imino forms. In the following formulas only one tautomeric form will be given, viz., the keto and the amino. 

Ckemicdl.—When heated, it is decomposed without fusion or sublimation. Its constitution is unknown. Heated in Cl it yields cyamiric acid and HCl. When Cl is passed for some time through H,0 holding uric acid in suspension, alloxan, parabanic and oxalic acids, and ammonium cyanate are formed. Similar decomposiUon is oduced by Br and L It is simply dissolved by HCl. It is dissolved by H,SO, from a hot solution ill which a deliquescent, crystalline compound, 4H SO is... 

The synthesis of uric acid has been accomplished by heating together a mixture of glycocol and urea at 230" (446° F)., and purifying the product. From this synthesis and from the products of decomposition of uric acid its constitution has been established. Its molecule consists of two urea remainders, CO(NH)s, united unsymmetrioally by a group of three carbon and one oxygen atoms, in the manner represented by the formula ... 

The examples which have been given to illustrate the methods employed to identify unknown substances, and to determine structure, have been selected on account of their simplicity and the readiness with which the observations recorded lead to definite conclusions. The steps involved in the study of many other compounds are equally obvious, but in the case of substances of more complicated structure the solution of the problem of their constitution is, at times, arrived at only after extended study. This is markedly true in the case of substances which do not contain the simple groups described up to this point. A number of important compounds which occur in nature contain their atoms linked in so-called rings and in other configurations. New principles must be developed before a conception of the structure of substances of this nature, such as uric acid, caffeine, and so forth, can be arrived at. A few examples will be given later. 

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. 

Barbituric acid has been known for over a century. In 1863 Adolf Baeyer published the first of a series of papers on the uric acid group [100]. The constitution of these ureido derivatives was then unknown. Baeyer proposed that they could most simply be grouped around the substance N2C4O3H4, which I will call barbituric acid In 1864, after a series of brilliant deductions... 

In similar stress experiments following therapy with orally administered vitamin B12, no significant differences were observed in the determinations before and after therapy. Consequently, adaptation to the stress was not the cause of the changes which occurred following pantothenate therapy. The decrease in the eosinopenia and in uric acid/ creatinine ratio after pantothenate treatment suggests that the same environmental stress constituted a less severe stimulus to the adrenal cortex under these conditions. It may be that the increased level of pantothenate in the tissue cells contributed to their capacity to carry out the oxidative reactions which are part of the total physiological response to cold stress. It is possible that under these conditions the demand for adrenocortical hormones might be somewhat reduced. 

Sanlu brand powdered milk was found to eontain significant amounts of melamine, with the highest coneentration being 2563 mg/kg of produet (0.2 %). The kidney stones in patients suffering from melamine were not melamine-cyanuric acid, but melamine and uric acid in 1 1.2-2.1 ratios (Fig. 2.11). Natural formation of uric acid kidney stones is not unknown, but they constitute only 5-10% of all kidney stones, especially in developing eountries. Babies excrete urie aeid in much... 

Wohler and Liebig prepared the derivatives of uric acid by fairly simple oxidation reactions with nitric acid etc., and reduction reactions, and speculated on the relations of the compounds and their constitution . Xanthic oxide they correctly found contains an atom of oxygen less than uric acid its present name xanthine was proposed by Gmelin, Allantoin was discovered by Buniva and Vauquelin and further investigated by Wohler. Wohler and Liebig obtained it by oxidising uric acid with a suspension of lead dioxide. 

This shows that caffeine contains three methyl groups and its constitution must resemble that of uric acid. 

The chemistry and metabolism of purines, pyrimidines, and their nucleosides and nucleotides constitute one of the oldest subjects of biochemistry, beginning as it does with the identification of uric acid in 1776. It is ironic that it has taken longer to work out the pathways of the synthesis, interconversion, and catabolism of these compounds than those of many other metabolites. 

RPs have been proposed for a relatively long time, and luce pictures are found in many books on electroanalysis, in order to sketch the redox mediation in compact or swollen, differently structured, polymer systems. However, in our opinion, this class of conductive polymers has attracted insufficient attention from electroanalysts. The number of newly synthesized RPs actually used as electrode materials for electroanalysis is much lower than reasonable, on the basis of the appealing characteristics of similar materials. One reason for this can undoubtedly be found in the widespread use of ICPs that, once suitably functionalized, constitute valid and often preferable alternatives to RPs. It is for Chap. 2 to complain about a similar deficiency in the frame of ICPs, which induces doubts about the actual validity of the explanation given here. Moreover, when amperometric sensing is taken into consideration, common benchmark analytes such as ascorbic acid or uric acid, in aqueous buffered solution, are considered. Less often, the study is widened to different analytes, and, even less fi-equently, the effectiveness of the systems in real matrices is evaluated. It is evident that the last studies would be of basic importance, since they point to specific interfering species and deal with true matrix effects, as to the presence of poisoning adsorbing species, possible speci-ation, etc. 

Within the general electrocatalytic scheme, in Ref. [23] PVP linking a 2,2 -bipyridine (bipy) complex, namely [Os(bipy)2] has also been characterized as to the behavior with respect to NOp reduction. An analytical application to the evaluation of NOp in river water was also proposed [24]. A similar polymer, cross-linked on purpose, is characterized and tested with respect to oxidation of uric acid present in urine [25]. The same [Os(bipy)2] group, coordinated to the imidazole residue of a PVl chain, deposited onto a microdisk electrode, has been characterized, and the behavior with respect to NADH oxidation has been defined as a preliminary step to the use in the frame of a biosensor [26]. Once more, an Os(lll)/ Os(ll) complex constituted the functionalization of a non-conducting polymer chain of an RP used as an electrode modification in the determination of ascorbic acid in urine, also in the presence of uric acid and dopamine as interfering species [27]. 

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