Uric Acid Metabolism

Abstract

Nitrogenous compounds are continuously derived from digestion of proteins in ingested food, degradation of nucleic acids, purine salvage pathways, de novo purine biosynthesis, and purine nucleotide interconversion. Nitrogenous waste products are highly toxic; therefore, efficient mechanisms of elimination have evolved, that are optimally suited for the particular class of organism. All animals excrete three main nitrogenous products – ammonia, urea and uric acid – as well as minor nitrogen excretory products.

Keywords: uric acid; ammonia; urea; purines; xanthine; oxidase; xanthinuria; gout; hyperuricemia

Figure 1.

Major pathways of purine metabolism. Highly toxic nitrogenous wastes are produced during purine metabolism. Efficient pathways for elimination of theses toxic wastes have evolved that are optimally suited for the particular class of organism.

Figure 2.

Clinical consequences of altered nucleotide metabolism. Clinical problems associated with nucleotide metabolism in humans are predominantly the result of abnormal catabolism of purine. The clinical consequences of abnormal purine metabolism range from mild to severe and even fatal disorders.

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References

Alfonzo JD, Sahota A and Taylor MW (1997) Purification and characterization of adenine phosphoribosyltransferase from Saccharomyces cerevisiae. Biochemica et Biophysica Acta 1341: 173–182.

Ichida K, Amaya Y, Kamatani N et al. (1997) Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria. Journal of Clinical Investigation 99: 2391–2397.

Kim TH, Lee HM, Utsonomiya H et al. (1997) Enhanced survival of transgenic hepatocytes expressing hepatocyte growth factor in hepatocyte tissue engineering. Transplantation Proceedings 29: 858–860.

Markert ML, Finkel BD, McLaughlin TM et al. (1997) Mutations in purine nucleoside phosphorylase deficiency. Human Mutation 9: 118–121.

Parks DA, Skinner KA, Skinner HB and Tan S (1998) Multiple organ dysfunction syndrome: role of xanthine oxidase and nitric oxide. Pathophysiology 5: 49–56.

Van Den Berghe G, Vincent MF and Jaeken J (1997) Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. Journal of Inherited Metabolic Disease 20: 193–202.

van der Vliet A, Smith D, O'Neill CA et al. (1994) Interactions of peroxynitrite with human plasma and its constituents: oxidative damage and antioxidant depletion. Biochemical Journal 303: 295–301.

Whelton A, Watson AJ and Rock RC (1994) Nitrogen metabolites and renal function. In: Burtis CA and Ashwood ER (eds) Tietz Textbook of Clinical Chemistry, 2nd ed. pp. 1513–1575. Philadelphia: WB Saunders

Wright PA (1995) Nitrogen excretion: three end products, many physiological roles. Journal of Experimental Biology 198: 273–281.

Wu X, Lee CC, Muzny DM and Caskey CT (1989) Urate oxidase: primary structure and evolutionary implications. Proceedings of the National Academy of Sciences of the USA 86: 9412–9416.

Further Reading

Alderman M and Aiyer KJV (2004) Uric acid: role in cardiovascular disease and effects of losartan. Current Medical Research and Opinion 20: 369–379.

Anker SD et al. (2003) Uric acid and survival in chronic heart failure – Validation and application in metabolic, functional, and hemodynamic staging. Circulation 107: 1991–1997.

Culleton BF, Larson MG, Kannel WB and Levy D (1999) Serum uric acid and risk for cardiovascular disease and death: the Framingham heart study. Annals of Internal Medicine 131: 7–+.

Davidson MB et al. (2004) Pathophysiology, clinical consequences, and treatment of tumor lysis syndrome. American Journal of Medicine 116: 546–554.

Hare JM and Johnson RJ (2003) Uric acid predicts clinical outcomes in heart failure ‐ insights regarding the role of xanthine oxidase and uric acid in disease pathophysiology. Circulation 107: 1951–1953.

Roch‐Ramel F and Guisan B (1999) Renal transport of urate in humans. News Physiol Sci. 14: 80–84.

Waring WS (2002) Uric acid: an important antioxidant in acute ischaemic stroke. Qjm‐An International Journal of Medicine 95: 691–693.

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Skinner, Kelly A, Parks, Dale A, and Khoo, Nicholas H(Jan 2006) Uric Acid Metabolism. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003910]