Uric acid metabolism in humans.

Abstract

U RIG ACID, the end product of purine degradation in humans, gains clinical significance during states of increased production, decreased elimination, or increased renal excretion. Under these conditions urate can be deposited in tissues, or uric acid can precipitate in urine to cause uric acid nephrolithiasis. Disorders associated with abnormal uric acid homeostasis include Lesch-Nyhan syndrome, an inherited enzyme deficiency, gout, renal insufficiency, and increased cellular breakdown as in tumor lysis. This article focuses on the sources, production, and elimination of uric acid in man. Uric acid is a weak acid with a pKal of 5.75 due to a proton loss at position 9. l At the physiologic pH range of human serum, uric acid is a monovalent ion, but in urine, which has a more acidic pH range, it is mostly excreted as the free acid. Thus, when uric acid is deposited in tissues, as seen in tophaceous gout, the deposits are mostly monosodium urate utilizing the most abundant cation, and uric acid renal stones are largely free acid.* Uric acid can also lose a second proton at position 3 with a pKa, of 10.3.3 The solubility of uric acid, like the ionization, is pH-dependent, increasing as the pH and urate formation increase.4 In urine, at a pH of 5 .O, uric acid is soluble to 15 mg/dL and increases with increasing pH to 1,520 mg/dL at a pH of 8.0.5 From this information, it is obvious to see why urine alkalinization is an important therapy to prevent or dissolve uric acid kidney stones. To fully understand the metabolism of uric acid, it is important to begin with the source of uric acid, purines. There are three sources of purines: (1) dietary intake of foods containing purine bases, (2) de novo endogenous synthesis from nonpurine precursors, and (3) salvage of purine bases from endogenous catabolism. The major source of dietary purine is protein. The average diet contains 70 to 100 g/d of proteins.6 Hyperuricemia is induced by a high dietary intake of meats containing nucleic acid and mononucleotides.7.8 Zollner reported the intestinal absorption of mononucleotides to be complete, and the absorption of ribonucleotides to be only