Uric acid
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Crystals of urate in polarized light
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Names | |||
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Preferred IUPAC name
7,9-Dihydro-1H-purine-2,6,8(3H)-trione | |||
Other names
2,6,8-Trioxypurine; 2,6,8-Trihydroxypurine; 2,6,8-Trioxopurine; 1H-Purine-2,6,8-trione
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Identifiers | |||
3D model (
JSmol ) |
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3DMet | |||
156158 | |||
ChEBI | |||
ChEMBL | |||
ChemSpider | |||
DrugBank | |||
ECHA InfoCard
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100.000.655 | ||
EC Number |
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IUPHAR/BPS |
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KEGG | |||
MeSH | Uric+Acid | ||
PubChem CID
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UNII | |||
CompTox Dashboard (EPA)
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Properties | |||
C5H4N4O3 | |||
Molar mass | 168.112 g·mol−1 | ||
Appearance | White crystals | ||
Melting point | 300 °C (572 °F; 573 K) | ||
6 mg/100 mL (at 20 °C) | |||
log P | −1.107 | ||
Acidity (pKa) | 5.6 | ||
Basicity (pKb) | 8.4 | ||
−6.62×10−5 cm3 mol−1 | |||
Thermochemistry | |||
Heat capacity (C)
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166.15 J K−1 mol−1 (at 24.0 °C) | ||
Std molar
entropy (S⦵298) |
173.2 J K−1 mol−1 | ||
Std enthalpy of (ΔfH⦵298)formation |
−619.69 to −617.93 kJ mol−1 | ||
Std enthalpy of (ΔcH⦵298)combustion |
−1921.2 to −1919.56 kJ mol−1 | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Uric acid is a
Chemistry
Uric acid was first isolated from
Uric acid displays lactam–lactim
Tautomers of uric acid and urate pKa1 Lactam form LactimformUrate ion
Water solubility
In general, the water
Solubility of urate salts (grams of water per gram of compound) Compound Cold water Boiling water Uric acid 15,000 2,000 Ammonium hydrogen urate — 1,600 Lithium hydrogen urate 370 39 Sodium hydrogen urate 1,175 124 Potassium hydrogen urate 790 75 Magnesium dihydrogen diurate 3,750 160 Calcium dihydrogen diurate 603 276 Disodium urate 77 — Dipotassium urate 44 35 Calcium urate 1,500 1,440 Strontium urate 4,300 1,790 Barium urate 7,900 2,700
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.[7][8][9]
Biochemistry
The enzyme
Genetic and physiological diversity
Primates
In
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[16] (but see below for slightly different values). An individual can have serum values as high as 96 mg/L and not have gout.[17] 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.[18] 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.[19]
Dogs
The
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.[21]
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.[22]
Genetics
Although foods such as meat and seafood can elevate serum urate levels, genetic variation is a much greater contributor to high serum urate.
Myogenic
AMP → IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid
Clinical significance and research
In human blood plasma, the reference range of uric acid is typically 3.4–7.2 mg per 100 mL(200–430 μmol/L) for men, and 2.4–6.1 mg per 100 mL for women (140–360 μmol/L).[31] Uric acid concentrations in blood plasma above and below the normal range are known as, respectively, hyperuricemia and hypouricemia. Likewise, uric acid concentrations in urine above and below normal are known as hyperuricosuria and hypouricosuria. Uric acid levels in saliva may be associated with blood uric acid levels.[32]
High uric acid
Hyperuricemia (high levels of uric acid), which induces gout, has various potential origins:
- Diet may be a factor. High intake of dietary
- Serum uric acid can be elevated by reduced excretion via the kidneys.[35]
- Fasting or rapid weight loss can temporarily elevate uric acid levels.[36]
- Certain drugs, such as renal clearance.[37]
- Tumor lysis syndrome, a metabolic complication of certain cancers or chemotherapy, due to nucleobase and potassium release into the plasma.[38]
- Pseudohypoxia (disrupted NADH/NAD+ ratio) caused by diabetic hyperglycemia and excessive alcohol consumption.[39]
Gout
A 2011 survey in the United States indicated that 3.9% of the population had gout, whereas 21.4% had hyperuricemia without having symptoms.[40]
Excess blood uric acid (serum urate) can induce gout,[41] a painful condition resulting from needle-like crystals of uric acid termed monosodium urate crystals[42] precipitating in joints, capillaries, skin, and other tissues.[43] Gout can occur where serum uric acid levels are as low as 6 mg per 100 mL (357 μmol/L), but an individual can have serum values as high as 9.6 mg per 100 mL (565 μmol/L) and not have gout.[17]
In humans, purines are metabolized into uric acid, which is then excreted in the urine. Consumption of large amounts of some types of purine-rich foods, particularly meat and seafood, increases gout risk.[44] Purine-rich foods include liver, kidney, and sweetbreads, and certain types of seafood, including anchovies, herring, sardines, mussels, scallops, trout, haddock, mackerel, and tuna.[45] Moderate intake of purine-rich vegetables, however, is not associated with an increased risk of gout.[44]
One treatment for gout in the 19th century was administration of
Tumor lysis syndrome
Lesch–Nyhan syndrome
Lesch–Nyhan syndrome, a rare inherited disorder, is also associated with high serum uric acid levels.[49] Spasticity, involuntary movement, and cognitive retardation as well as manifestations of gout are seen in this syndrome.[50]
Cardiovascular disease
Hyperuricemia is associated with an increase in
Uric acid stone formation
Saturation levels of uric acid in blood may result in one form of
Diabetes
Hyperuricemia is associated with components of metabolic syndrome, including in children.[56][57]
Low uric acid
Low uric acid (
Multiple sclerosis
Meta-analysis of 10 case-control studies found that the serum uric acid levels of patients with multiple sclerosis were significantly lower compared to those of healthy controls, possibly indicating a diagnostic biomarker for multiple sclerosis.[60]
Normalizing low uric acid
Correcting low or deficient zinc levels can help elevate
See also
- Theacrine or 1,3,7,9-tetramethyluric acid, a purine alkaloid found in some teas
- Uracil – purine nucleobase named by Robert Behrend who was attempting to synthesize derivatives of uric acid
- Metabolic myopathy
- Purine nucleotide cycle
References
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