Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the method C5H4N4O3. It kinds ions and salts often known as urates and acid urates, similar to ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it’s a regular part of urine. Excessive blood concentrations of uric acid can result in gout and are related to different medical circumstances, together with diabetes and the formation of ammonium acid urate kidney stones.
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Chemistry[edit]
Uric acid was first remoted from kidney stones in 1776 by the Swedish chemist Carl Wilhelm Scheele.[1] In 1882, the Ukrainian chemist Ivan Horbaczewski first synthesized uric acid by melting urea with glycine.[2]
Uric acid shows lactam–lactim tautomerism (additionally typically described as keto–enol tautomerism[3]). Though the lactim type is anticipated to own a point of aromaticity, uric acid crystallizes within the lactam type,[4] with computational chemistry additionally indicating that tautomer to be probably the most steady.[5]
Uric acid is a diprotic acid with pKa1 = 5.4 and pKa2 = 10.3,[6] thus at physiological pH, it predominately exists because the monoionic urate ion.
Water Solubility[edit]
Basically, the water solubility of uric acid and its alkali metallic and alkaline earth salts is reasonably low. All these salts exhibit better solubility in sizzling water than chilly, permitting for straightforward recrystallization. This low solubility is critical for the etiology of gout. The solubility of the acid and its salts in ethanol could be very low or negligible. In ethanol/water mixtures, the solubilities are someplace between the top values for pure ethanol and pure water.
The figures given point out what mass of water is required to dissolve a unit mass of compound indicated. The decrease the quantity the extra soluble the substance within the stated solvent.[7][8][9]
Biochemistry[edit]
Xanthine oxidase is an enzyme which catalyzes the formation of uric acid from xanthine and hypoxanthine, which in flip are produced from different purines. Xanthine oxidase is a big enzyme whose energetic website consists of the metallic molybdenum certain to sulfur and oxygen.[10] Inside cells, xanthine oxidase can exist as xanthine dehydrogenase and xanthine oxireductase, which has additionally been purified from bovine milk and spleen extracts.[11] Uric acid is launched in hypoxic circumstances (low oxygen saturation).[12]
Genetic and physiological range[edit]
Primates. In people and better primates, uric acid (really hydrogen urate ion) is the ultimate oxidation (breakdown) product of purine metabolism and is excreted in urine, whereas in most different mammals, the enzyme uricase additional oxidizes uric acid to allantoin.[13] The lack of uricase in greater primates parallels the same lack of the flexibility to synthesize ascorbic acid, resulting in the suggestion that urate could partially substitute for ascorbate in such species.[14] Each uric acid and ascorbic acid are sturdy lowering brokers (electron donors) and potent antioxidants. In people, over half the antioxidant capability of blood plasma comes from hydrogen urate ion.[15]
People. The traditional focus vary of uric acid (or hydrogen urate ion) in human blood is 25 to 80 mg/L for males and 15 to 60 mg/L for ladies[16] (however see under for barely totally different values). A person can have serum values as excessive as 96 mg/L and never have gout.[17] In people, about 70% of every day uric acid disposal happens by way of the kidneys, and in 5–25% of people, impaired renal (kidney) excretion results in hyperuricemia.[18] Regular excretion of uric acid within the urine is 250 to 750 mg per day (focus of 250 to 750 mg/L if one litre of urine is produced per day – greater than the solubility of uric acid as a result of it’s within the type of dissolved acid urates).
Canine. The Dalmatian canine has a genetic defect in uric acid uptake by the liver and kidneys, leading to decreased conversion to allantoin, so this breed excretes uric acid, and never allantoin, within the urine.[19]
Birds and reptiles. In birds and reptiles, and in some desert dwelling mammals (such because the kangaroo rat), uric acid is also the end-product of purine metabolism, however it’s excreted in feces as a dry mass. This includes a posh metabolic pathway that’s energetically expensive compared to processing of different nitrogenous wastes similar to urea (from the urea cycle) or ammonia, however has some great benefits of lowering water loss and stopping dehydration.[20]
Invertebrates. Platynereis dumerilii, a marine polychaete worm, makes use of uric acid as a sexual pheromone. The feminine of the species releases uric acid into the water throughout mating, to induce males to launch sperm.[21]
Genetics[edit] – “calcium urate”
Though meals similar to meat and seafood can elevate serum urate ranges, genetic variation is a a lot better contributor to excessive serum urate.[22][23]
A proportion of individuals have mutations within the proteins liable for the excretion of uric acid by the kidneys. Variants inside plenty of genes have up to now been recognized: SLC2A9; ABCG2; SLC17A1; SLC22A11; SLC22A12; SLC16A9; GCKR; LRRC16A; and PDZK1.[24][25][26] SLC2A9 is thought to move each uric acid and fructose.[18][27]
Medical significance and analysis[edit]
In human blood plasma, the reference vary of uric acid is often 3.4–7.2 mg per 100 mL (200–430 μmol/L) for males, and a couple of.4–6.1 mg per 100 mL for ladies (140–360 μmol/L).[28] Uric acid concentrations in blood plasma above and under the traditional vary are often known as, respectively, hyperuricemia and hypouricemia. Likewise, uric acid concentrations in urine above and under regular are often known as hyperuricosuria and hypouricosuria. Uric acid ranges in saliva could also be related to blood uric acid ranges.[29]
Excessive uric acid[edit]
Hyperuricemia (excessive ranges of uric acid), which induces gout, has varied potential origins:
Gout[edit]
A 2011 survey in america indicated that 3.9% of the inhabitants had gout, whereas 21.4% had hyperuricemia with out having signs.[36]
Extra blood uric acid can induce gout,[37] a painful situation ensuing from needle-like crystals of uric acid precipitating in joints, capillaries, pores and skin, and different tissues.[38] Gout can happen the place serum uric acid ranges are as little as 6 mg per 100 mL (357 μmol/L), however a person can have serum values as excessive as 9.6 mg per 100 mL (565 μmol/L) and never have gout.[17]
In people, purines are metabolized into uric acid which is then excreted within the urine. Consumption of some kinds of purine-rich meals, significantly meat and seafood, will increase gout danger.[39] Gout could come up from common consumption of meats, similar to liver, kidney, and sweetbreads, and sure kinds of seafood together with anchovies, herring, sardines, mussels, scallops, trout, haddock, mackerel and tuna.[40] Average consumption of purine-rich greens, nevertheless, shouldn’t be related to an elevated danger of gout.[39]
One therapy for gout within the nineteenth century was administration of lithium salts;[41] lithium urate is extra soluble. Right now, irritation throughout assaults is extra generally handled with NSAIDs, colchicine, or corticosteroids, and urate ranges are managed with allopurinol.[42] Allopurinol, which weakly inhibits xanthine oxidase, is an analog of hypoxanthine that’s hydroxylated by xanthine oxidoreductase on the 2-position to provide oxipurinol.[43]
Tumor lysis syndrome[edit]
Tumor lysis syndrome, an emergency situation that will consequence from blood cancers, produces excessive uric acid ranges in blood when tumor cells launch their contents into the blood, both spontaneously or following chemotherapy.[35] Tumor lysis syndrome could result in acute kidney damage when uric acid crystals are deposited within the kidneys.[35] Therapy consists of hyperhydration to dilute and excrete uric acid by way of urine, rasburicase to cut back ranges of poorly soluble uric acid in blood, or allopurinol to inhibit purine catabolism from including to uric acid ranges.[35]
Lesch–Nyhan syndrome[edit]
Lesch–Nyhan syndrome, a uncommon inherited dysfunction, can also be related to excessive serum uric acid ranges.[44] Spasticity, involuntary motion, and cognitive retardation in addition to manifestations of gout are seen on this syndrome.[45]
Heart problems[edit]
Hyperuricemia could improve danger components for heart problems.[46]
Sort 2 diabetes[edit]
Hyperuricemia could also be a consequence of insulin resistance in diabetes reasonably than its precursor.[47] One research confirmed excessive serum uric acid was related to greater danger of sort 2 diabetes, unbiased of weight problems, dyslipidemia, and hypertension.[48] Hyperuricemia is related to parts of metabolic syndrome, together with in kids.[49][50]
Uric acid stone formation[edit]
Kidney stones can type by means of deposits of sodium urate microcrystals.[51][52]
Saturation ranges of uric acid in blood could lead to one type of kidney stones when the urate crystallizes within the kidney. These uric acid stones are radiolucent and so don’t seem on an belly plain X-ray.[53] Uric acid crystals may promote the formation of calcium oxalate stones, appearing as “seed crystals”.[54]
Low uric acid[edit]
Low uric acid (hypouricemia) can have quite a few causes. Low dietary zinc intakes trigger decrease uric acid ranges. This impact will be much more pronounced in girls taking oral contraceptive remedy.[55] Sevelamer, a drug indicated for prevention of hyperphosphataemia in folks with power kidney failure, can considerably cut back serum uric acid.[56]
A number of sclerosis[edit]
Meta-analysis of 10 case-control research discovered that the serum uric acid ranges of sufferers with a number of sclerosis had been considerably decrease in comparison with these of wholesome controls, presumably indicating a diagnostic biomarker for a number of sclerosis.[57]
Normalizing low uric acid[edit]
Correcting low or poor zinc ranges can assist elevate serum uric acid.[58]
See additionally[edit]