Uric acid balance
- Michael A Becker, MD
Michael A Becker, MD
- Section Editor — Crystal Diseases
- Professor Emeritus of Medicine
- University of Chicago Pritzker School of Medicine
Uric acid is the end product of the metabolism of purine compounds. With a (functional) pKa of about 5.75 in blood (5.35 in urine), the reaction
Uric acid <—> Urate- + H+
is shifted far to the right at the normal arterial pH of 7.40. As a result, most uric acid circulates as the urate anion.
The vast majority of mammalian species have extremely low serum urate levels (about 1 mg/dL; 60 micromol/L) because uric acid is converted to allantoin, a highly soluble excretory product. By contrast, uric acid is the end product of purine metabolism in humans, because the human homolog of the mammalian uricase (urate oxidase) gene is structurally modified to an unexpressed (pseudogene) state. Thus, normal humans have serum urate concentrations approaching the theoretical limit of solubility of urate in serum (6.8 mg/dL) and regularly excrete urine that is supersaturated with respect to uric acid. As an example, the mean serum urate concentration was formerly reported to be between 5 and 6 mg/dL among healthy adult white men in the United States, and the prevalence of hyperuricemia in this group was estimated to be at least 5 to 8 percent. However, subsequent epidemiologic data from the National Health and Nutrition Examination Survey 2007 to 2008 indicate that hyperuricemia (as defined in that study by a single urate determination exceeding 7 mg/dL) is much more prevalent, occurring in up to 21.4 percent of adults in the surveyed US adult population . (See "Asymptomatic hyperuricemia".)
The normal adult male has a total body urate pool of approximately 1200 mg, about twice that of the normal adult female. This gender difference may be explained by an enhancement of renal urate excretion in women of childbearing age due to the effects of estrogenic compounds , which likely reduce the number of active renal urate transporters, resulting in lesser renal tubular uric acid reabsorption and thus increased urate clearance . Normally, all urate measured in the body pool is believed to be soluble urate. When insoluble urate crystal deposition occurs (in gout), body pool measurements underestimate the body urate pool. Under normal steady state conditions, daily turnover of about 60 percent of the urate pool is achieved by balanced production and elimination of uric acid.
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