Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.
Chemistry Uric acid was first isolated from kidney stones in 1776 by Swedish chemist Carl Wilhelm Scheele. In 1882, the Ukrainian chemist Ivan Horbaczewski first synthesized uric acid by melting urea with glycine. Uric acid displays lactam–lactim tautomerism. Uric acid crystallizes in the lactam form, with computational chemistry also indicating that tautomer to be the most stable. Uric acid is a diprotic acid with pKa1 = 5.4 and pKa2 = 10.3. At physiological pH, urate predominates in solution.
Biochemistry The enzyme xanthine oxidase (XO) catalyzes the formation of uric acid from xanthine and hypoxanthine. XO, which is found in mammals, functions primarily as a dehydrogenase and rarely as an oxidase, despite its name. Xanthine in turn is produced from other purines. Xanthine oxidase is a large enzyme whose active site consists of the metal molybdenum bound to sulfur and oxygen. Uric acid is released in hypoxic conditions (low oxygen saturation).
Water solubility In general, the water solubility of uric acid and its alkali metal and alkaline earth salts is rather low. All these salts exhibit greater solubility in hot water than cold, allowing for easy recrystallization. This low solubility is significant for the etiology of gout. The solubility of the acid and its salts in ethanol is also very low or negligible.
The figures given indicate what mass of water is required to dissolve a unit mass of compound indicated. The lower the number, the more soluble the substance in the said solvent.
Fructose-related uric acid production Under conditions of an ordinary diet with low levels of fructose consumed, uric acid production is negligible. When fructose consumption is excessive, uric acid levels can increase via an unregulated fructokinase pathway that consumes ATP and converts fructose into fructose-1-phosphate, leading to the degradation of AMP into uric acid. Other factors possibly contributing to increased risk of hyperuricemia include alcohol consumption, obesity, male sex, and aging.
Genetic and physiological diversity
Primates In hominids uric acid (actually hydrogen urate ion) is the final oxidation (breakdown) product of purine metabolism and is excreted in urine, whereas in most other mammals, the enzyme uricase further oxidizes uric acid to allantoin. The loss of uricase in higher primates parallels the similar loss of the ability to synthesize the soluble vitamin vitamin C (ascorbic acid), suggesting that urate may partially substitute for ascorbate in such species. Both uric acid and ascorbic acid are strong reducing agents (electron donors) and potent antioxidants. In humans, over half the antioxidant capacity of blood plasma comes from hydrogen urate ion. Genetic studies of more primates have found that the loss of uricase activity did not happen at the same time as the loss of L-gulonolactone oxidase (GLUO) activity (vitamin C synthesis), with approximately 30 million years between the two events, suggesting that one did not immediately lead to another. More specifically, loss of uricase happened in hominids while loss of GLUO also affected monkeys. Instead, it was hypothesized that the increase in uric acid blood levels was beneficial to apes as it promotes the conversion of fructose to triglycerides, allowing them to store energy for longer. In 2025, it was confirmed that when human liver cells are made to produce an ancestral uricase via CRISPR, they do not produce more triglyceride when taking up fructose.
Humans The normal concentration range of uric acid (or hydrogen urate ion) in human blood is 25 to 80 mg/L for men and 15 to 60 mg/L for women (but see below for slightly different values). An individual can have serum values as high as 96 mg/L and not have gout. In humans, about 70% of daily uric acid disposal occurs via the kidneys, and in 5–25% of humans, impaired renal (kidney) excretion leads to hyperuricemia. Normal excretion of uric acid in the urine is 270 to 360 mg per day (concentration of 270 to 360 mg/L if one litre of urine is produced per day – higher than the solubility of uric acid because it is in the form of dissolved acid urates), roughly 1% as much as the daily excretion of urea.
Dogs The Dalmatian has a genetic defect in uric acid uptake by the liver and kidneys, resulting in decreased conversion to allantoin, so this breed excretes uric acid, and not allantoin, in the urine.
Birds, reptiles and desert-dwelling mammals In birds and reptiles, and in some desert-dwelling mammals (such as the kangaroo rat), uric acid also is the end product of purine metabolism, but it is excreted in feces as a dry mass. This involves a complex metabolic pathway that is energetically costly in comparison to processing of other nitrogenous wastes such as urea (from the urea cycle) or ammonia, but has the advantages of reducing water loss and preventing dehydration.
Invertebrates Platynereis dumerilii, a marine polychaete worm, uses uric acid as a sexual pheromone. The female of the species releases uric acid into the water during mating, which induces males to release sperm.
Bacteria Uric acid metabolism is done in the human gut by ~1/5 of bacteria species that come from 4 of 6 major phyla. Such metabolism is anaerobic involving uncharacterized ammonia lyase, peptidase, carbamoyl transferase, and oxidoreductase enzymes. The result is that uric acid is converted into xanthine or lactate and the short chain fatty acids such as acetate and butyrate. Radioisotope studies suggest about 1/3 of uric acid is removed in healthy people in their gut with this being roughly 2/3 in those with kidney disease. In uricase-deficient mouse models, such bacteria compensate for the loss of uricase and keep the increase in urate levels in check. Removal of these bacteria turns the hyperuricemia severe in these mice, leading researchers to raise the possibility "that antibiotics targeting anaerobic bacteria, which would ablate gut bacteria, increase the risk for developing gout in humans".
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