Skip to main content

Uric Acid Metabolism in Humans

  • Chapter
  • First Online:
Gout
  • 2285 Accesses

Abstract

The material reviewed in Chap. 3 is expanded in detail. Sources of uric acid in humans, from diet and from human metabolism, explain how elevated quantities of the end product of purine metabolism in humans, uric acid, occur. Genetic and other factors leading to hyperuricemia in humans are described as well.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gutman AB, Yu TF. Renal function in gout: with a commentary on the renal regulation of urate excretion and the role of the kidney in the pathogenesis of gout. Am J Med. 1957;23:600.

    Article  PubMed  CAS  Google Scholar 

  2. Seegmiller JE, Grayzel AI, Laster L, Liddle L. Uric acid production in gout. J Clin Invest. 1961;40:1304.

    Article  PubMed  CAS  Google Scholar 

  3. Benedict JD, Yu T-F, Bien EJ, Gutman AB, Stetten Jr D. A further study of the utilization of dietary glycine nitrogen for uric acid synthesis in gout. J Clin Invest. 1953;32:775.

    Article  PubMed  CAS  Google Scholar 

  4. Benedict JD, Roche M, Yu T-F, Bien EJ, Gutman AB, Stetten Jr D. Incorporation of glycine nitrogen into uric acid in normal and gouty man. Metabolism. 1952;1:3.

    PubMed  CAS  Google Scholar 

  5. Wyngaarden JB. Overproduction of uric acid as the cause for hyperuricemia in primary gout. J Clin Invest. 1957;36:1508.

    Article  PubMed  CAS  Google Scholar 

  6. Wyngaarden JB. Normal glycine-C14 incorporation into uric acid in primary gout. Metabolism. 1958;7:374.

    PubMed  CAS  Google Scholar 

  7. Emmerson BT. The effect of weight reduction on urate metabolism. In: Sperling O, DeVreis A, Wyngaarden JB, editors. Purine metabolism in man, vol. 41B. New York: Plenum; 1974. p. 429.

    Google Scholar 

  8. Yu T-F, Roboz J. Long-term follow-up of incorporation of 15N from glycine into uric acid in gout. Am J Med. 1981;70:797.

    Article  PubMed  CAS  Google Scholar 

  9. Wyngaarden JB, Kelley WN. Gout and hyperuricemia. New York: Grune and Stratton; 1976. p. 1–512.

    Google Scholar 

  10. Wyngaarden JB, Kelley WN. Gout. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, editors. The metabolic basis of inherited disease. 4th ed. New York: McGraw-Hill; 1978. p. 916.

    Google Scholar 

  11. Scott JT, Holloway VP, Glass HI, Arnot RN. Studies of uric acid pool size and turnover rate. Ann Rheum Dis. 1969;28:366.

    Article  PubMed  CAS  Google Scholar 

  12. Benedict JD, Forsham PH, Roche M, Sotoway J, Stetten Jr D. The effect of salicylates and adrenocorticotropic hormone on the miscible pool of uric acid in gout. J Clin Invest. 1950;29:1104.

    Article  PubMed  CAS  Google Scholar 

  13. Sorenson LB. The pathogenesis of gout. Arch Intern Med. 1962;109:379.

    Article  Google Scholar 

  14. Kelley WN, Greene ML, Rosenbloom FM, Henderson JF. Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann Intern Med. 1969;70:155.

    PubMed  CAS  Google Scholar 

  15. Wyngaarden JB, Kelley WN. Gout. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, editors. The metabolic basis of inherited disease. 5th ed. New York: McGraw-Hill Book Company; 1983. 1078p.

    Google Scholar 

  16. DeVries A, Sperling O. Familial gouty malignant uric acid lithiasis due to mutant phosphoribosylpyrophosphate synthetase. Urologe A. 1973;12:153.

    CAS  Google Scholar 

  17. Hershko A, Hershko C, Mager J. Increased formation of 5′-phosphoribosyl-1-pyrophosphate in red blood cells of some gouty patients. Isr J Med Sci. 1968;4:939.

    PubMed  CAS  Google Scholar 

  18. Becker MA, Losman MJ, Wilson J, Simmonds HA. Superactivity of human phosphoribosylpyrophosphate synthetase due to altered regulation by nucleotide inhibitors and inorganic phosphate. Biochim Biophys Acta. 1986;882:168.

    Article  PubMed  CAS  Google Scholar 

  19. Becker MA, Meyer LJ, Wood AW, Seegmiller JE. Purine overproduction in man associated with increased phosphoribosylpyrophosphate synthetase activity. Science. 1973;179:1123.

    Article  PubMed  CAS  Google Scholar 

  20. Becker MA. Patterns of phosphoribosylpyrophosphate and ribose-5-phosphate concentration and generation in fibroblasts from patients with gout and purine overproduction. J Clin Invest. 1976;57:308.

    Article  PubMed  CAS  Google Scholar 

  21. Cohen JL, Vinik A, Fuller J, Fox IH. Hyperuricemia in glycogen storage disease type I: contributions by hypoglycemia and hypophosphatemia to increased urate production. J Clin Invest. 1985;78:251.

    Article  Google Scholar 

  22. Tsalikian E, Simmons P, Howard C, Haymond MW. Near normal glucose production in type I GSD. Pediatr Res. 1982;16:265A.

    Google Scholar 

  23. Slonim AE, Lacy WW, Terry A, Greene HL, Burr IM. Nocturnal intragastric therapy in type I glycogen storage disease: effect on hormonal and amino acid metabolism. Metab Clin Exp. 1979;28:707.

    Article  PubMed  CAS  Google Scholar 

  24. Crigler JF, Folkman J. Glycogen storage disease: new approaches to therapy. Ciba Found Symp. 1978;55:331.

    Google Scholar 

  25. Greene HL, Slonim AE, O’Neill JA, Burr IM. Continuous nocturnal intragastric feeding for management of type I glycogen storage disease. N Engl J Med. 1976;294:423.

    Article  PubMed  CAS  Google Scholar 

  26. Davisdon AGF, Wong TK, Kirby L, Tze WJ, Rigg JM, Applegarth DA. Glycogen storage disease type I: effect of continuous nocturnal nasogastric feeding. Monogr Hum Genet. 1978;9:29.

    Google Scholar 

  27. Ehrlich RM, Robinson BH, Freedman HH, Howard NJ. Nocturnal intragastric infusion of glucose in management of defective gluconeogenesis with hypoglycemia. Am J Dis Child. 1978;132:241.

    PubMed  CAS  Google Scholar 

  28. Pearlman M, Aker M, Slonim AE. Successful treatment of severe type I glycogen storage disease with neonatal presentation by nocturnal intragastric feeding. J Pediatr. 1979;94:772.

    Article  Google Scholar 

  29. Greene HL, Slonim AE, Burr IM, Moran JR. Type I glycogen storage disease: five years of management with nocturnal intragastric feeding. J Pediatr. 1980;96:590.

    Article  PubMed  CAS  Google Scholar 

  30. Benke PJ, Gold S. Uric acid metabolism in therapy of glycogen storage disease type I. Pediatr Res. 1978; 12:204.

    Article  PubMed  CAS  Google Scholar 

  31. Burchell A. Molecular pathology of glucose-6-­phosphatase. FASEB J. 1990;4:2978.

    PubMed  CAS  Google Scholar 

  32. Dunger DB, Holton JB. Disorders of carbohydrate metabolism. In: Hommes FA, editor. Techniques in diagnostic human biochemical genetics: a laboratory manual. New York: Wiley-Liss; 1991. p. 21.

    Google Scholar 

  33. Mineo I, Kono N, Hara N, Shimizu T, Yamada Y, Kawachi M, Kiyokawa H, Wang YL, Tarui S. Myogenic hyperuricemia. A common pathophysiologic feature of glycogenoses types III, V, and VII. N Engl J Med. 1987;317:75.

    Article  PubMed  CAS  Google Scholar 

  34. Nakagawa C, Mineo I, Kaido M, Fujimura H, Shimizu T, Hamaguchi T, Nakajima H, Tarui S. A new variant case of muscle phosphofructokinase deficiency, coexisting with gastric ulcer, gouty arthritis, and increased hemolysis. Muscle Nerve Suppl. 1995;3:S39–44.

    Article  CAS  Google Scholar 

  35. Bertorini TE, Shively V, Taylor B, Palmieri GMA, Fox IH. ATP degradation products after ischemic exercise: hereditary lack of phosphylase or carnitine palmityltransferase. Neurology. 1985;35:1355.

    Article  PubMed  CAS  Google Scholar 

  36. Sabina RL, Swain JL, Olanow CW, Bradley WG, Fishbein WN, DiMauro S, Holmes EW. Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle. J Clin Invest. 1984;73:720.

    Article  PubMed  CAS  Google Scholar 

  37. DiMauro S, Miranda AF, Khan S, Gitlin K, Friedman R. Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy. Science. 1981;212:1277.

    Article  PubMed  CAS  Google Scholar 

  38. DiMauro S, Miranda AF, Hays AP, et al. Myoadenylate deaminase deficiency: muscle biopsy and muscle culture in a patient with gout. J Neurol Sci. 1980;47:191.

    Article  PubMed  CAS  Google Scholar 

  39. Puig JG, Fox IH. Ethanol induced activation of adenine nucleotide turnover. Evidence for a role of acetate. J Clin Invest. 1984;74:936.

    Article  PubMed  CAS  Google Scholar 

  40. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest. 1985;76:1713.

    Article  PubMed  CAS  Google Scholar 

  41. Fox IH. Metabolic basis for disorders of purine nucleotide degradation. Metabolism. 1981;30:616.

    Article  PubMed  CAS  Google Scholar 

  42. Grum CM, Simon RH, Dantzker DR, Fox IH. Biochemical indicators of cellular hypoxia in critically ill patients: evidence for ATP degradation. Chest. 1985;88:763.

    Article  PubMed  CAS  Google Scholar 

  43. Woolliscroft JO, Colfer H, Fox IH. Hyperuricemia in acute illness: a poor prognostic sign. Am J Med. 1982;72:58.

    Article  PubMed  CAS  Google Scholar 

  44. Woolliscroft JO, Fox IH. Increased body fluid purines during hypotensive events: evidence for ATP degradation. Am J Med. 1986;81:472.

    Article  PubMed  CAS  Google Scholar 

  45. Yu T-F, Weismann B, Sharney L, et al. On the biosynthesis of uric acid from glycine-N15 in primary and secondary polycythemia. Am J Med. 1956;21:901.

    Article  PubMed  Google Scholar 

  46. Yu T-F, Wasserman LR, Benedict J, et al. A simultaneous study of glycine-N15 incorporation into uric acid and heme, and of Fe utilization, in a case of gout associated with polycythemia secondary to congenital heart disease. Am J Med. 1953;15:845.

    Article  PubMed  CAS  Google Scholar 

  47. Lester L, Muller AF. Uric acid production in a case of myeloid metaplasia associated with gouty arthritis, studied with N15-labeled glycine. Am J Med. 1953; 15:857.

    Article  Google Scholar 

  48. Wyngaarden JB. Intermediary purine metabolism and the metabolic defects of gout. Metabolism. 1957;6:244.

    PubMed  CAS  Google Scholar 

  49. Wyngaarden JB, Blair AE, Hilley L. On the mechanism of overproduction of uric acid in patients with primary gout. J Clin Invest. 1958;37:579.

    Article  PubMed  CAS  Google Scholar 

  50. Bauman RR, Jillson OF. Hyperuricemia and psoriasis. J Invest Dermatol. 1961;36:105.

    Google Scholar 

  51. Eisen AZ, Seegmiller JE. Uric acid metabolism in psoriasis. J Clin Invest. 1961;40:1486.

    Article  PubMed  CAS  Google Scholar 

  52. Mariani G, Tuoni M, Gianfaldoni R, Molea N, Giubbolini L, Fusani L, Mian E, Bianchi R. Turnover and distribution of 14C-uric acid in psoriatic patients. Adv Exp Med Biol. 1984;165A:277.

    Article  Google Scholar 

  53. Puig JG, Mateos FA, Jimenez ML, Gomez PL, Michan AA, Vazquez JO. Uric acid metabolism in psoriasis. Adv Exp Med Biol. 1986;195A:411–6.

    Article  Google Scholar 

  54. Lambert JR, Wright V. Serum uric acid levels in psoriatic arthritis. Ann Rheum Dis. 1977;36:264–7.

    Article  PubMed  CAS  Google Scholar 

  55. Brenner W, Gschnait F. Serum uric acid levels in untreated and PUVA-treated patients with psoriasis. Dermatologica. 1978;157:91–5.

    Article  PubMed  CAS  Google Scholar 

  56. Sutton JR, Toews CJ, Ward GR, Fox IH. Purine metabolism during strenuous muscle exercise in man. Metabolism. 1980;29:254.

    Article  PubMed  CAS  Google Scholar 

  57. Nasralla S, Al-Khalidi V. Nature of purines excreted in urine during muscular exercise. J Appl Physiol. 1964;19:246.

    Google Scholar 

  58. Knochel JB, Dotin LN, Hamburger RJ. Heat stress, exercise, and muscle injury: effects on urate metabolism. Ann Intern Med. 1972;81:321.

    Google Scholar 

  59. Grantham JJ, Chonko AM. Renal handling of organic anions and cations; metabolism and excretion of uric acid. In: Brenner BM, editor. The kidney. 3rd ed. Philadelphia: Saunders; 1986. p. 663.

    Google Scholar 

  60. van den Berghe G, Hers HG. Abnormal AMP deaminase in primary gout. Lancet. 1980;2:1090.

    PubMed  Google Scholar 

  61. Abe M, Higuchi I, Morisaki H, et al. Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutation I AMPD1 gene: case report of a Japanese patient. Neuromuscul Disord. 2000;10:472.

    Article  PubMed  CAS  Google Scholar 

  62. Morisaki H, Morisaki T, Newby LK, Holmes EW. Alternative splicing: a mechanism for phenotype rescue of a common inherited defect. J Clin Invest. 1993;91:2275.

    Article  PubMed  CAS  Google Scholar 

  63. Morisaki H, Morisaki T, Kariko K, et al. Positive and negative elements mediate control of alternative splicing in the AMPD1 gene. Gene. 2000;246:365.

    Article  PubMed  CAS  Google Scholar 

  64. Goldfinger S, Klinenberg JR, Sigmiller JE. Renal retention of uric acid induced by infusion of beta-hydroxybutyrate and acetoacetate. N Engl J Med. 1965;272:351.

    Article  PubMed  CAS  Google Scholar 

  65. Yu T-F, Sirota JH, Berger L, Halpern M, Gutman AB. Effect of sodium lactate infusion on urate clearance in man. Proc Soc Exp Biol (NY). 1957;96:809–13.

    CAS  Google Scholar 

  66. Schulman JD, Lustberg TJ, Kennedy JL, Museles M, Seegmiller JE. A new variant of maple syrup urine disease (branched chain ketoaciduria): clinical and biochemical evaluation. Am J Med. 1970;49:118.

    Article  PubMed  CAS  Google Scholar 

  67. Yu T-F, Gutman AB. Study of the paradoxical effects of salicylates in low, intermediate, and high dosage on the renal mechanisms for excretion of urate in man. J Clin Invest. 1959;38:1298.

    Article  PubMed  CAS  Google Scholar 

  68. Gutman AB, Yu T-F. Renal mechanisms for the regulation of uric acid excretion, with special reference to normal and gouty man. Semin Arthritis Rheum. 1972;2:1.

    Article  PubMed  CAS  Google Scholar 

  69. Campion DW, Olsen RW, Caughey D, Bluestone R, Klinenberg JR. Does increased free serum urate concentration cause gout? Clin Res. 1975;23:261.

    Google Scholar 

  70. Nugent CA, Tyler FH. The renal excretion of uric acid in patients with gout and in nongouty subjects. J Clin Invest. 1959;38:1890.

    Article  PubMed  CAS  Google Scholar 

  71. Seegmiller JE, Grayzel AL, Howell RR, et al. The renal excretion of uric acid in gout. J Clin Invest. 1962;41:1094.

    Article  PubMed  CAS  Google Scholar 

  72. Yu T-F, Berger L, Gutman AB. Renal function in gout. II. Effect of uric acid loading on renal excretion of uric acid. Am J Med. 1962;33:829.

    Article  PubMed  CAS  Google Scholar 

  73. Latham W, Rodnan JP. Impairment of uric acid excretion in gout. J Clin Invest. 1962;41:1955.

    Article  Google Scholar 

  74. Rieselbach RE, Steele TH. Influence of the kidney upon urate homeostasis in health and disease. Am J Med. 1974;56:665.

    Article  PubMed  CAS  Google Scholar 

  75. Diamond HS, Paolino JS. Evidence for a post-secretory reabsorptive site for uric acid in man. J Clin Invest. 1973;52:1491.

    Article  PubMed  CAS  Google Scholar 

  76. Steele TH. Urate secretion in man: the pyrazinamide suppression test. Ann Intern Med. 1973;79:734.

    PubMed  CAS  Google Scholar 

  77. Reiselbach RE, Sorenson LB, Shelp WD, Steele TH. Diminished renal urate secretion per nephron as a basis for primary gout. Ann Intern Med. 1970;73:359.

    Google Scholar 

  78. Puig JG, Anton FM, Jimenez ML, Guitierrez PC. Renal handling of uric acid in gout: impaired tubular transport of urate not dependent on serum urate values. Metabolism. 1986;35:1147.

    Article  Google Scholar 

  79. Puig JG, Anton FM, Sanz MA, Gaspar G, Lesmes A, Ramos T, Vazquez OJ. Renal handling of uric acid in normal subjects by means of the pyrazinamide and probenecid tests. Nephron. 1983;35:183.

    Article  Google Scholar 

  80. Levinson DJ, Sorenson LB. Renal handling of uric acid in gouty and normal subjects: evidence for a 4-component system. Ann Rheum Dis. 1980;39:173.

    Article  PubMed  CAS  Google Scholar 

  81. Ross GR, Seegmiller JE. Hyperuricemia and gout. N Engl J Med. 1979;300:1459.

    Article  Google Scholar 

  82. Steele TH, Rieselbach RE. The contribution of residual nephrons within the chronically diseased kidney to urate homeostasis in man. Am J Med. 1967;43:876.

    Article  PubMed  CAS  Google Scholar 

  83. Feinstein EI, Quion VH, Kaptein EM, Massry SG. Severe hyperuricemia in patients with volume depletion. Am J Nephrol. 1984;4:77.

    Article  PubMed  CAS  Google Scholar 

  84. Steele TH. Evidence for altered renal urate reabsorption during changes in volume of the extracellular fluid. J Lab Clin Med. 1969;74:228.

    Google Scholar 

  85. Suki WN, Eknoyan G, Martinez-Maldonado M. Tubular sites and mechanisms action of diuretics. Annu Rev Pharmacol. 1973;13:91.

    Article  PubMed  CAS  Google Scholar 

  86. Steele TH, Oppenheimer S. Factors affecting urate excretion following diuretic administration in man. Am J Med. 1969;47:564.

    Article  PubMed  CAS  Google Scholar 

  87. Goldfinger S, Klinenberg JR, Seegmiller JE. Renal retention of uric acid induced by infusion of beta-hydroxybutyrate and acetoacetate. N Engl J Med. 1965;272:351.

    Article  PubMed  CAS  Google Scholar 

  88. Menon RK, Mikhailidis DP, Bell JL, Kernoff PB, Daddona P. Warfarin administration increases uric acid concentrations in the plasma. Clin Chem. 1986;32:1557.

    PubMed  CAS  Google Scholar 

  89. Sugino H, Kagoshima M, Katagiri S. Effects of some drugs on plasma uric acid in rats – actions of catecholamines and beta-blocking agents. Nippon Yakurigaku Zasshi. 1984;84:293.

    Article  PubMed  CAS  Google Scholar 

  90. Palestine AG, Nussenblatt RB, Chan CC. Side effects of systemic cyclosporine in patients not undergoing transplantation. Am J Med. 1984;77:652.

    Article  PubMed  CAS  Google Scholar 

  91. Hamilton WFD, Robertson GS. Changes in serum uric acid related to the dose of methoxyflurane. Br J Anaesth. 1974;46:54.

    Article  PubMed  CAS  Google Scholar 

  92. Weiner IM, Tinker JP. Pharmacology of pyrazinamide: metabolic and renal function studies related to the mechanism of drug-induced urate retention. J Pharmacol Exp Ther. 1972;180:411.

    PubMed  CAS  Google Scholar 

  93. Postlethwaite AB, Bartel AG, Kelley WN. Hyperuricemia due to ethambutol. N Engl J Med. 1972;286:761.

    Article  PubMed  CAS  Google Scholar 

  94. Gershon SL, Fox IH. Pharmacologic effects of nicotinic acid on human purine metabolism. J Lab Clin Med. 1974;84:179.

    PubMed  CAS  Google Scholar 

  95. Becker MA, Raivio KO, Meyer LJ, Seegmiller JE. The effects of nicotinic acid on human purine metabolism. Clin Res. 1973;21:616.

    Google Scholar 

  96. Honda H, Gindin RA. Gout while receiving levodopa for Parkinsonism. JAMA. 1972;219:55.

    Article  PubMed  CAS  Google Scholar 

  97. Morita Y, Nishida Y, Kamatani N, Miyamoto T. Theophylline increases serum uric acid levels. J Allergy Clin Immunol. 1984;74:707.

    Article  PubMed  CAS  Google Scholar 

  98. Titinen S, Nissila M, Ruutsalo HM, Isomaki H. Effect of nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid. Clin Rheumatol. 1983;2:233.

    Article  Google Scholar 

  99. Batuman V, Maesaka JK, Haddad B, Tepper E, Landy E, Wedeen RP. The role of lead in gout nephropathy. N Engl J Med. 1981;304:520.

    Article  PubMed  CAS  Google Scholar 

  100. Ball GV, Sorenson LB. Pathogenesis of hyperuricemia in saturnine gout. N Engl J Med. 1969;280:1199.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Newcombe, D.S. (2013). Uric Acid Metabolism in Humans. In: Robinson, D. (eds) Gout. Springer, London. https://doi.org/10.1007/978-1-4471-4264-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4264-5_4

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4263-8

  • Online ISBN: 978-1-4471-4264-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics