Uric acid metabolism in man

This workshop included reviews from some of the leading authorities on the various aspects of uric acid metabolism in man biochemistry, pathology, renal handling, nutrition, etc., and these reviews and results of new studies are presented here. 

Further reading Balls, M.E. (1976). Uric acid metabolism in man. In Bodansky, O. and Latner, A.L. (eds.) Advances in Clinical Chemistry. Vol. 18. p. 213. (New York Academic Press)... 

Gershon, S and Fox, I. H. Effects of nicotinic acid on uric acid metabolism in man. Arth. Rheum. (Abstract) (in press). 

As an inhibitor of xanthine oxidase, allopurinol also markedly decreases oxidation of both hypoxanthine and xanthine itself to the sole source of uric acid (19) in man. This metabolic block thus removes the source of uric acid that in gout causes the painful crystalline deposits in the joints. It is of interest that allopurinol itself is oxidized to the somewhat less effective drug, oxypurinol (21), by xanthine oxidase. 

Renal excretion of uric acid consists of three components complete filterability of uric acid in the glomerulus, subsequent tubular reabsorption, and tubular secretion (Gutman and Yu 1961). Pronounced species differences have been described in uric acid metabolism including man. Mice were recommended for primary screening of uricosuric drugs. 

Bowering, J., Olloway, D.H., Margen, S., Kaufmann, N. A. Dietary protein level and uric acid metabolism in normal man. J. Nutr. 100 249 (1969). 

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. 

Uric acid is one of the principal products of purine metabolism in man 12 13). However, in many other organisms further oxidative degradation of the purine molecule occurs. One of the most important enzymes involved in uric acid oxidation is uricase, which has been studied to some extent in vitro. 

Uric acid is the end product of purine metabolism in man. Consequently, abnormal levels of uric acid serve to indicate disorders of metabolism of purines or nucleic acids. Serum levels of uric acid range from 200 to 420 pmol/L In males 15 to 20% and 3 to 4% of females suffer from hyperuricaemia. 

Although uric acid is the end product of purine metabolism in man and higher apes and the end product of nitrogen metabolism as a whole in some other animals, many higher organisms convert it to nonpurine derivatives. 

It has already been stated that uric acid is the principal end product of purine metabolism in man and the higher primates, while allantoin is formed in other mammals. Other groups in the animal kindgom also have characteristic end products allantoic acid, urea, or ammonia. This pattern is, of course, due to the phylogenetic distribution of the various enzymes involved in uric acid catabolism, and a very generalized picture of this distribution is shown in Table lO-I (S3). 

PURINE METABOLISM IN MAN Biochemistry and Pharmacology of Uric Acid Metabolism Edited by O. Sperling, A. De Vries, and J. B. Wyngaarden 1974... 

Purine metabolism in man biochemistry and pharmacology of uric acid metabolism. 

Interrelation of uric acid and ethanol metabolism in man. J. Clin. Invest. 1863-1870. 

Uric acid, O6H4N4OJ, the most important of the oxidised purines, is the chief end-product of purine metabolism in man and the higher apes. It is the chief end-product of protein metabolism in uricotelic animals, birds and snakes, and some invertebrates. It is the least soluble of all the forms in which nitrogen is excreted, and appears in calculi, articular deposits, and urinary sediments. 

In the case of the methylated xanthines, particularly theophylline, theobromine and caffeine, the preponderance of data on the metabolism of these compounds in man suggests that a methylated uric acid is the principal product. However, the data presented earlier proposes at best a 77 per cent accounting of the methylated xanthine administered. The question can be raised as to whether the final products observed upon electrochemical oxidation of these compounds aids these studies. Very recently studies of metabolism of caffeine have revealed that 3,6,8-trimethylallantoin is a metabolite of caffeine 48>. This methylated allantoin is, of course, a major product observed electrochemically. The mechanism developed for the electrochemical oxidation seems to nicely rationalize the observed products and electrochemical behavior. The mechanism of biological oxidation could well be very similar, although insufficient work has yet been performed to come to any definite conclusions. There is however, one major difference between the electrochemical and biological reactions which is concerned with the fact that in the former situation no demethylation occurs whereas in the latter systems considerable demethylation appears to take place. 

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