URIC ACID AND RELATED COMPOUNDS

Uric Acid, C5H4O3N4, occurs in small quantity in normal urine a man excretes daily about 0.7 grams of the acid. In gout, uric acid is deposited in the joints and under the skin as a difficultly soluble acid salt. It also occurs in the form of urinary calculi in the bladder. The ammonium salt of uric acid is the chief constituent of the excrement of birds and reptiles. The acid is most conveniently prepared from guano or the excrement of snakes. 

Uric acid is difficultly soluble in water at 18.5° one part of acid dissolves in 10,000 parts of water. It is a weak dibasic acid, which forms two series of salts. The normal sodium salt has the composition CBH203N4Na2.H20, and is soluble in 62 parts of water at room temperature. The acid salt, 2(C6H303-N4Na).H20, is soluble in about 1100 parts of water at 15°. Normal lithium urate is moderately soluble in water on account of this fact lithia-water has been suggested as a remedy for gout. 

Conclusions as to the structure of uric acid have been arrived at from the study of the products formed as the result of the oxidation of the acid. Among the oxidation-products are par-abanic acid and alloxan, which are formed when uric acid is treated with nitric acid, and allantoine, which results from the oxidation of the acid with potassium permanganate. The structure of these substances must be studied before an understanding of the configuration of uric acid can be reached. 

Parabanic Acid, C3H2N2O3.—Under certain conditions an acid of this formula is obtained by oxidizing uric acid with nitric acid. The structure of parabanic acid is deduced from the decomposition which results when the acid is hydrolyzed by an alkali urea and oxalic acid are formed — 

In this reaction parabanic acid resembles an amide oxamide yields oxalic acid and ammonia on hydrolysis — 

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The ability of the body to metabolize, or break down, lactic acid is decreased significantly by alcohol, which impairs the liver s ability to carry out normal metabolic reactions. Thus, alcoholics often have sore muscles from lactic acid build up that was not caused by exercise. Lactic acid can also lead to a build-up of uric acid crystals in the joints, since lactic acid reduces the elimination of uric acid and related compounds. This build-up can lead to gout, a very painful disease. 

B17. Bergmaim, F., and Dikstein, S., Studies on uric acid and related compounds. 

Xanthine oxidase catalyzes the oxidation of hypox-anthine and xanthine to uric acid. Xanthine oxidase is a complex metalloflavoprotein containing one molybdenum, one FAD and two iron-sulfur centers of the ferredoxine type in each of its two independent subunits. Usually, the enzyme is isolated from cow s milk. The enzyme is inhibited by allopurinol and related compounds. The production of uric acid from the substrate (xanthine) can be determined by measuring the change in optical density in the UV range. 

A book dealing with alkaloids in foods contains an account on caffeine and related compounds. The synthesis of caffeine, the conversion of uric acid into xanthine, and various syntheses of related heterocyclic compounds form subject matters in a review of broad scope. The role of purine alkaloids in trace-metal metabolism, disease resistance, mutagenesis, and chemotaxonomic considerations in plants has been reviewed. 

Samanidou, V.F. Metaxa, A.S. Papadoyannis, l.N. Direct simultaneous determination of uremic toxins Creatine, creatinine, uric acid, and xanthine in human biofluids by HPLC. J. Liq. Chromatogr. Relat. Technol. 2002,25 (1), 43 57. Abreo, K. Gautreaux, S. de Smet, R. Vogeleere, P. Ringoir, S. van Holdre, R. p-Cresol, a urinary compound, enhances the uptake of aluminum in hepatocytes. J. Am. Soc. Nephrol. 1997, 8 (6), 935-942. 

The evidence for the essentiality of molybdenum is substantial and conclusive. Molybdenum functions as a cofactor in enzymes that catalyze the hydroxylation of various substrates. Aldehyde oxidase oxidizes and detoxifies various pyrimidines, purines, pteridines, and related compounds. Xanthine oxidase/dehydrogenase catalyzes the transformation of hypoxanthine to xanthine, and xanthine to uric acid. Sulfite oxidase catalyzes the transformation of sulfite to sulfate. Attempts to produce molybdenum deficiency signs in rats, chickens, and humans have resulted in only limited success, and no success in healthy humans. 

Nitrogen compounds commonly determined are creatinine, urea, and uric acid. Creatinine is an end product of the energy process occurring within the muscles, and is thus related to muscle mass. Creatinine in urine is commonly used as an indicator and correction factor of dilution in urine. Creatinine in serum is an indicator of the filtration capacity of the kidney. Urea is the end product of the nitrogen luea cycle, starting with carbon dioxide and ammonia, and is the bulk compoimd of urine. The production of uric acid is associated with the disease gout. In some cases, it appears that the excess of uric acid is a consequence of impaired renal excretion of this substance. 

Enzyme-based biosensors are very suitable for the antioxidant status evaluation, since they show excellent selectivity for biological substances and can directly determine and/or monitor antioxidant compounds in a complex media such as biological or vegetable samples without needing a prior separation step. During the course of the catalytic reaction on the electroactive substrates, the current produced at an applied potential is related to the concentration of a specific biomarker, for which the biosensor is selective. HRP-based biosensors for antioxidant status evaluation have been applied in the detection of superoxide radical [119], nitric oxide [120], glutathione [119, 121], uric acid [122, 123], and phenolic compounds [124—126],... 

When the necessary data for substitution in these empirical relations are not available, the heat of vaporization must be estimated by analogy, or frankly guessed. For example, Pauling and Sherman give the heats of formation in the gas phase of a number of compounds such as uric acid, for which the estimate of the heats of vaporization can only be guesses of unknown accuracy. This may introduce errors of as much as 10 kcal, in the most unfavourable case, and Pauling and Sherman are careful not to draw conclusions from differences less than this. 

Among other naturally occurring compounds with an imidazole or reduced imidazole nucleus are biotin (208), the essential growth factor, the hydantoin (209) which occurs in beet sap, and allantoin (210) which is related to uric acid. 

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 ... 

Uric acid is associated with urea, creatine and creatinine in urine. In the urine of mammals it occurs in small amounts, the chief nitrogen compound being urea. In birds and reptiles, however, uric acid predominates and is the precursor of the related guanine in guano. 

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. 

A group of very interesting naturally occurring compounds are known which are nitrogenous basic substances and which are related to uric acid. They are ... 

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. 

Various papers related to the simultaneous determination of creatinine and uric acid can be found in the hterature. Several authors have developed capillary zone electrophoresis (CZE) methods for simultaneous analysis of these compounds in urine. The CE analysis of these renal markers offers some advantages when compared with chromatography, such as shortened separation time, reduced reagent consumption, and increased resolution. Capillar micellar electrokinetic chromatography has been applied to the simultaneous separation of creatinine and uric acid in human plasma and urine. However, chromatographic techniques are widely accepted for the determination of these compounds. Reversed-phase and ion... 

The term alkaloid is applied to certain nitrogenous constituents of plants. The alkaloids differ widely in structure some like muscarine (218) are aliphatic compounds, others like caffeine (418) contain a ring of carbon atoms and are related to uric acid. The alkaloids which are described briefly here are related to heterocyclic compounds, chiefly pyridine, quinoline. 

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. 

Various papers related to the simultaneous determination of creatinine and uric acid can be found in the literature. Several authors have developed CZE methods for the simultaneous analysis of these compounds in urine. The... 

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