Uric acid

Last updated

Contents

Uric acid
Harnsaure Ketoform.svg
Uric acid3D.png
Names
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
Identifiers
3D model (JSmol)
3DMet
156158
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.655 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 200-720-7
KEGG
MeSH Uric+Acid
PubChem CID
UNII
  • InChI=1S/C5H4N4O3/c10-3-1-2(7-4(11)6-1)8-5(12)9-3/h5,12H,(H,9,10)(H,7,8,11) X mark.svgN
    Key: DZGSAURIFGGOJK-UHFFFAOYSA-N X mark.svgN
  • lactam form:O=C1Nc2nc(=O)nc2C(=O)N1
  • intermediate form:Oc0nc(O)nc1c0NC(=O)N1
  • lactim form:Oc0nc(O)nc1c0N=C(O)N1
  • urate monoanion:Oc0nc(O)nc1c0N=C([O-])N1
Properties
C5H4N4O3
Molar mass 168.112 g·mol−1
AppearanceWhite 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
166.15 J K−1 mol−1 (at 24.0 °C)
Std molar
entropy (S⦵298)
173.2 J K−1 mol−1
−619.69 to −617.93 kJ mol−1
−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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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. [1] 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. [2] In 1882, the Ukrainian chemist Ivan Horbaczewski first synthesized uric acid by melting urea with glycine. [3]

Uric acid displays lactam–lactim tautomerism. [4] Uric acid crystallizes in the lactam form, [5] with computational chemistry also indicating that tautomer to be the most stable. [6] Uric acid is a diprotic acid with pKa1  = 5.4 and pKa2 = 10.3. [7] At physiological pH, urate predominates in solution.[ medical citation needed ]

Lactam ion, a stable tautomer of uric acid Harnsaure Ketoform.svg
Lactam ion, a stable tautomer of uric acid
Urate ion, a conjugate base of uric acid Urat.svg
Urate ion, a conjugate base of uric acid

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. [8] 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. [9] Uric acid is released in hypoxic conditions (low oxygen saturation). [10]

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 very low or negligible. In ethanol/water mixtures, the solubilities are somewhere between the end values for pure ethanol and pure water.[ medical citation needed ]

Solubility of urate salts (grams of water per gram of compound)
CompoundCold waterBoiling water
Uric acid15,0002,000
Ammonium hydrogen urate—1,600
Lithium hydrogen urate37039
Sodium hydrogen urate1,175124
Potassium hydrogen urate79075
Magnesium dihydrogen diurate3,750160
Calcium dihydrogen diurate603276
Disodium urate77—
Dipotassium urate4435
Calcium urate1,5001,440
Strontium urate4,3001,790
Barium urate7,9002,700

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. [11] [12] [13]

Genetic and physiological diversity

Primates

In humans 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. [14] The loss of uricase in higher primates parallels the similar loss of the ability to synthesize ascorbic acid, leading to the suggestion that urate may partially substitute for ascorbate in such species. [15] 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. [16]

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 [17] (but see below for slightly different values). An individual can have serum values as high as 96 mg/L and not have gout. [18] 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. [19] 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. [20]

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. [21]

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. [22]

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. [23]

Bacteria

Uric acid metabolism is done in the human gut by ∼1/5 of bacteria species hat 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. [24] 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. [25] In mouse models, such bacteria compensate for the loss of uricase leading researchers to raise the possibility "that antibiotics targeting anaerobic bacteria, which would ablate gut bacteria, increase the risk for developing gout in humans". [24]

Genetics

Although foods such as meat and seafood can elevate serum urate levels, genetic variation is a much greater contributor to high serum urate. [26] [27] A proportion of people have mutations in the urate transport proteins responsible for the excretion of uric acid by the kidneys. Variants of a number of genes, linked to serum urate, have so far been identified: SLC2A9 ; ABCG2 ; SLC17A1 ; SLC22A11 ; SLC22A12 ; SLC16A9 ; GCKR ; LRRC16A ; and PDZK1 . [28] [29] [30] GLUT9, encoded by the SLC2A9 gene, is known to transport both uric acid and fructose. [19] [31] [32]

Myogenic hyperuricemia, as a result of the purine nucleotide cycle running when ATP reservoirs in muscle cells are low, is a common pathophysiologic feature of glycogenoses, such as GSD-III, which is a metabolic myopathy impairing the ability of ATP (energy) production for muscle cells. [33] In these metabolic myopathies, myogenic hyperuricemia is exercise-induced; inosine, hypoxanthine and uric acid increase in plasma after exercise and decrease over hours with rest. [33] Excess AMP (adenosine monophosphate) is converted into uric acid.[ medical citation needed ]

AMP → IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid[ medical citation needed ]

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). [34] 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. [35]

High uric acid

Hyperuricemia (high levels of uric acid), which induces gout, has various potential origins:

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. [43]

Excess blood uric acid (serum urate) can induce gout, [44] a painful condition resulting from needle-like crystals of uric acid termed monosodium urate crystals [45] precipitating in joints, capillaries, skin, and other tissues. [46] 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. [18]

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. [47] Purine-rich foods include liver, kidney, and sweetbreads, and certain types of seafood, including anchovies, herring, sardines, mussels, scallops, trout, haddock, mackerel, and tuna. [48] Moderate intake of purine-rich vegetables, however, is not associated with an increased risk of gout. [47]

One treatment for gout in the 19th century was administration of lithium salts; [49] lithium urate is more soluble. Today, inflammation during attacks is more commonly treated with NSAIDs, colchicine, or corticosteroids, and urate levels are managed with allopurinol. [50] Allopurinol, which weakly inhibits xanthine oxidase, is an analog of hypoxanthine that is hydroxylated by xanthine oxidoreductase at the 2-position to give oxipurinol. [51]

Tumor lysis syndrome

Tumor lysis syndrome, an emergency condition that may result from blood cancers, produces high uric acid levels in blood when tumor cells release their contents into the blood, either spontaneously or following chemotherapy. [41] Tumor lysis syndrome may lead to acute kidney injury when uric acid crystals are deposited in the kidneys. [41] Treatment includes  hyperhydration to dilute and excrete uric acid via urine, rasburicase to reduce levels of poorly soluble uric acid in blood, or  allopurinol to inhibit purine catabolism from adding to uric acid levels. [41]

Lesch–Nyhan syndrome

Lesch–Nyhan syndrome, a rare inherited disorder, is also associated with high serum uric acid levels. [52] Spasticity, involuntary movement, and cognitive retardation as well as manifestations of gout are seen in this syndrome. [53]

Cardiovascular disease

Hyperuricemia is associated with an increase in risk factors for cardiovascular disease. [54] It is also possible that high levels of uric acid may have a causal role in the development of atherosclerotic cardiovascular disease, but this is controversial and the data are conflicting. [55]

Uric acid stone formation

Comparison of different types of urinary crystals. Urine crystals comparison.png
Comparison of different types of urinary crystals.

Kidney stones can form through deposits of sodium urate microcrystals. [56]

Saturation levels of uric acid in blood may result in one form of kidney stones when the urate crystallizes in the kidney. These uric acid stones are radiolucent, so do not appear on an abdominal plain X-ray. [57] Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seed crystals". [58]

Diabetes

Hyperuricemia is associated with components of metabolic syndrome, including in children. [59] [60]

Low uric acid

Low uric acid (hypouricemia) can have numerous causes. Low dietary zinc intakes cause lower uric acid levels. This effect can be even more pronounced in women taking oral contraceptive medication. [61] Sevelamer, a drug indicated for prevention of hyperphosphataemia in people with chronic kidney failure, can significantly reduce serum uric acid. [62]

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. [63]

Normalizing low uric acid

Correcting low or deficient zinc levels can help elevate serum uric acid. [64]

See also

Related Research Articles

<span class="mw-page-title-main">Gout</span> Form of arthritis causing swollen joints

Gout is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crystals. Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours. The joint at the base of the big toe is affected (Podagra) in about half of cases. It may also result in tophi, kidney stones, or kidney damage.

<span class="mw-page-title-main">Xanthine oxidase</span> Class of enzymes

Xanthine oxidase is a form of xanthine oxidoreductase, a type of enzyme that generates reactive oxygen species. These enzymes catalyze the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid. These enzymes play an important role in the catabolism of purines in some species, including humans.

<span class="mw-page-title-main">Allopurinol</span> Medication

Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken orally or intravenously.

<span class="mw-page-title-main">Hyperuricemia</span> Excess uric acid in the blood

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for males, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off (lysed) from the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias and in particular when treating non-Hodgkin lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia. This is a potentially fatal complication and patients at increased risk for TLS should be closely monitored while receiving chemotherapy and should receive preventive measures and treatments as necessary. TLS can also occur on its own although this is less common.

<span class="mw-page-title-main">Urate oxidase</span> Pseudogene in the species Homo sapiens

The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:

<span class="mw-page-title-main">Lesch–Nyhan syndrome</span> Rare genetic disorder

Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the HPRT1 gene located on the X chromosome. LNS affects about 1 in 380,000 live births. The disorder was first recognized and clinically characterized by American medical student Michael Lesch and his mentor, pediatrician William Nyhan, at Johns Hopkins.

<span class="mw-page-title-main">Rasburicase</span> Pharmaceutical drug

Rasburicase, sold under the brand name Elitek in the US and Fasturtec in the EU, is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is known to be present in many mammals but does not naturally occur in humans. Rasburicase is produced by a genetically modified Saccharomyces cerevisiae strain. The complementary DNA (cDNA) coding for rasburicase was cloned from a strain of Aspergillus flavus.

<span class="mw-page-title-main">Glycogen storage disease type I</span> Medical condition

Glycogen storage disease type I is an inherited disease that prevents the liver from properly breaking down stored glycogen, which is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. There are also possibly rarer subtypes, the translocases for inorganic phosphate or glucose ; however, a recent study suggests that the biochemical assays used to differentiate GSD Ic and GSD Id from GSD Ib are not reliable, and are therefore GSD Ib.

Protein toxicity is the effect of the buildup of protein metabolic waste compounds, like urea, uric acid, ammonia, and creatinine. Protein toxicity has many causes, including urea cycle disorders, genetic mutations, excessive protein intake, and insufficient kidney function, such as chronic kidney disease and acute kidney injury. Symptoms of protein toxicity include unexplained vomiting and loss of appetite. Untreated protein toxicity can lead to serious complications such as seizures, encephalopathy, further kidney damage, and even death.

Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule of the kidney. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms.

<span class="mw-page-title-main">Probenecid</span> Chemical compound

Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.

<span class="mw-page-title-main">Hypouricemia</span> Lack of uric acid in the blood

Hypouricemia or hypouricaemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 μmol/L (6 mg/dL) for women and 619 μmol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign of a medical condition.

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">Hyperuricosuria</span> Excess uric acid in the urine

Hyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. For men this is at a rate greater than 800 mg/day, and for women, 750 mg/day. Notable direct causes of hyperuricosuria are dissolution of uric acid crystals in the kidneys or urinary bladder, and hyperuricemia. Notable indirect causes include uricosuric drugs, rapid breakdown of bodily tissues containing large quantities of DNA and RNA, and a diet high in purine.

<span class="mw-page-title-main">SLC22A12</span> Mammalian protein found in Homo sapiens

Solute carrier family 22, member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12 gene.

A xanthine oxidase inhibitor is any substance that inhibits the activity of xanthine oxidase, an enzyme involved in purine metabolism. In humans, inhibition of xanthine oxidase reduces the production of uric acid, and several medications that inhibit xanthine oxidase are indicated for treatment of hyperuricemia and related medical conditions including gout. Xanthine oxidase inhibitors are being investigated for management of reperfusion injury.

<span class="mw-page-title-main">Topiroxostat</span> Chemical compound

Topiroxostat is a drug for the treatment of gout and hyperuricemia. It was approved for use in Japan in June 2013.

<span class="mw-page-title-main">Lesinurad</span> Pharmaceutical drug for the treatment of gout

Lesinurad is a urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is recommended only as an adjuvant with either allopurinol or febuxostat when these medications are not sufficient.

<span class="mw-page-title-main">Gout suppressants</span> Drugs to control and prevent gout attacks

Gout suppressants are agents which control and prevent gout attacks after the first episode. They can be generally classified into two groups by their purpose: drugs used for induction therapy and that for maintenance therapy.

References

  1. ↑ "Uric Acid". PubChem.
  2. ↑ Scheele, C. W. (1776). "Examen Chemicum Calculi Urinari" [A chemical examiniation of kidney stones]. Opuscula. 2: 73.
  3. ↑ Horbaczewski, J. (1882). "Synthese der Harnsäure" [Synthesis of uric acid]. Monatshefte für Chemie und Verwandte Teile Anderer Wissenschaften. 3: 796–797. doi:10.1007/BF01516847. S2CID   92323943.
  4. ↑ Lieberman, M.; Marks, A. D.; Smith, C. M.; Marks, D. B. (2007). Marks' Essential Medical Biochemistry . Philadelphia: Lippincott Williams & Wilkins. pp.  47–. ISBN   978-0-7817-9340-7.
  5. ↑ Ringertz, H. (1 March 1966). "The molecular and crystal structure of uric acid". Acta Crystallographica. 20 (3): 397–403. Bibcode:1966AcCry..20..397R. doi: 10.1107/S0365110X66000914 .
  6. ↑ Jiménez, V.; Alderete, J. B. (November 2005). "Theoretical calculations on the tautomerism of uric acid in gas phase and aqueous solution". Journal of Molecular Structure: THEOCHEM. 755 (1–3): 209–214. doi:10.1016/j.theochem.2005.08.001.
  7. ↑ McCrudden, F. H. (2008) [1905]. Uric Acid: The Chemistry, Physiology and Pathology of Uric Acid and the Physiologically Important Purin Bodies, with a Discussion of the Metabolism in Gout. Charleston, SC: BiblioBazaar. ISBN   978-0-554-61991-0.
  8. ↑ Ichida, K.; Amaya, Y.; Noda, K.; Minoshima, S.; Hosoya, T.; Sakai, O.; Shimizu, N.; Nishino, T. (November 1993). "Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): Structural analysis of the protein and chromosomal location of the gene". Gene. 133 (2): 279–284. doi:10.1016/0378-1119(93)90652-J. PMID   8224915.
  9. ↑ Hille, R. (2005). "Molybdenum-containing hydroxylases". Archives of Biochemistry and Biophysics. 433 (1): 107–116. doi:10.1016/j.abb.2004.08.012. PMID   15581570.
  10. ↑ Baillie, J. K.; Bates, M. G.; Thompson, A. A.; Waring, W. S.; Partridge, R. W.; Schnopp, M. F.; Simpson, A.; Gulliver-Sloan, F.; Maxwell, S. R.; Webb, D. J. (May 2007). "Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude". Chest. 131 (5): 1473–1478. doi:10.1378/chest.06-2235. PMID   17494796.
  11. ↑ Weast, R. C., ed. (1981). CRC Handbook of Chemistry and Physics (62nd ed.). Boca Raton, FL: CRC Press. OCLC   7842683.
  12. ↑ Windholz, M., ed. (1976). Merck Index (9th ed.). Merck. ISBN   978-0-911910-26-1.
  13. ↑ McCrudden, Francis H. Uric acid. p. 58.
  14. ↑ Angstadt, C. N. (4 December 1997). "Purine and Pyrimidine Metabolism: Purine Catabolism". NetBiochem.
  15. ↑ Proctor, P. (November 1970). "Similar functions of uric acid and ascorbate in man?". Nature. 228 (5274): 868. Bibcode:1970Natur.228..868P. doi: 10.1038/228868a0 . PMID   5477017. S2CID   4146946.
  16. ↑ Maxwell, S. R. J.; Thomason, H.; Sandler, D.; Leguen, C.; Baxter, M. A.; Thorpe, G. H. G.; Jones, A. F.; Barnett, A. H. (1997). "Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus". European Journal of Clinical Investigation. 27 (6): 484–490. doi:10.1046/j.1365-2362.1997.1390687.x. PMID   9229228. S2CID   11773699.
  17. ↑ Braunwald, E., ed. (1987). Harrison's Principles of Internal Medicine (11th ed.). New York: McGraw-Hill. p. A-3. ISBN   978-0-07-079454-2.
  18. 1 2 Tausche, A. K.; Unger, S.; Richter, K.; et al. (May 2006). "Hyperurikämie und Gicht" [Hyperuricemia and gout: diagnosis and therapy]. Der Internist (in German). 47 (5): 509–521. doi:10.1007/s00108-006-1578-y. PMID   16586130. S2CID   11480796.
  19. 1 2 Vitart, V.; Rudan, I.; Hayward, C.; et al. (April 2008). "SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout". Nature Genetics. 40 (4): 437–442. doi:10.1038/ng.106. PMID   18327257. S2CID   6720464.
  20. ↑ Kaur, P.; Bhatt, H. (2022). "Hyperuricosuria". StatPearls. StatPearls. PMID   32965872.
  21. ↑ Friedman, M. & Byers, S. O. (1 September 1948). "Observations concerning the causes of the excess excretion of uric acid in the Dalmatian dog". The Journal of Biological Chemistry. 175 (2): 727–735. doi: 10.1016/S0021-9258(18)57191-X . PMID   18880769.
  22. ↑ Hazard, L. C. (2004). Sodium and Potassium Secretion by Iguana Salt Glands. Iguanas: Biology and Conservation. University of California Press. pp. 84–85. ISBN   978-0-520-23854-1.
  23. ↑ Zeeck, E.; Harder, T.; Beckmann, M. (1998). "Uric acid: the sperm-release pheromone of the marine polychaete Platynereis dumerilii". Journal of Chemical Ecology. 24 (1): 13–22. doi:10.1023/A:1022328610423. S2CID   42318049.
  24. 1 2 Liu, Yuanyuan; Jarman, J. Bryce; Low, Yen S.; Augustijn, Hannah E.; Huang, Steven; Chen, Haoqing; DeFeo, Mary E.; Sekiba, Kazuma; Hou, Bi-Huei; Meng, Xiandong; Weakley, Allison M.; Cabrera, Ashley V.; Zhou, Zhiwei; van Wezel, Gilles; Medema, Marnix H.; Ganesan, Calyani; Pao, Alan C.; Gombar, Saurabh; Dodd, Dylan (2023). "A widely distributed gene cluster compensates for uricase loss in hominids". Cell. 186 (16): 3400–3413.e20. doi: 10.1016/j.cell.2023.06.010 . ISSN   0092-8674.
  25. ↑ Sorensen, Leif B. (1965). "Role of the intestinal tract in the elimination of uric acid". Arthritis & Rheumatism. 8 (4). Wiley: 694–706. doi:10.1002/art.1780080429. ISSN   0004-3591.
  26. ↑ Major, T. J.; Topless, R. K.; Merriman, T. R. (2018). "Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts". The BMJ . 363: k3951. doi:10.1136/bmj.k3951. PMC   6174725 . PMID   30305269.
  27. ↑ Keenan, R. T. (2020). "The biology of urate". Seminars in Arthritis and Rheumatism. 50 (35): S2–S10. doi: 10.1016/j.semarthrit.2020.04.007 . PMID   32620198.
  28. ↑ Aringer, M.; Graessler, J. (December 2008). "Understanding deficient elimination of uric acid". Lancet. 372 (9654): 1929–1930. doi:10.1016/S0140-6736(08)61344-6. PMID   18834627. S2CID   1839089.
  29. ↑ Kolz, M.; Johnson, T.; et al. (June 2009). Allison, David B. (ed.). "Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations". PLOS Genet. 5 (6): e1000504. doi: 10.1371/journal.pgen.1000504 . PMC   2683940 . PMID   19503597.
  30. ↑ Köttgen, A.; et al. (February 2013). "Genome-wide association analyses identify 18 new loci associated with serum urate concentrations" (PDF). Nature Genetics. 45 (2): 145–154. doi:10.1038/ng.2500. PMC   3663712 . PMID   23263486.
  31. ↑ Döring, A.; Gieger, C.; Mehta, D.; et al. (April 2008). "SLC2A9 influences uric acid concentrations with pronounced sex-specific effects". Nature Genetics. 40 (4): 430–436. doi:10.1038/ng.107. PMID   18327256. S2CID   29751482.
  32. ↑ Mandal, Asim K.; Mount, David B. (February 2015). "The molecular physiology of uric acid homeostasis". Annual Review of Physiology . 77: 323–345. doi:10.1146/annurev-physiol-021113-170343. PMID   25422986.
  33. 1 2 Mineo, Ikuo; Kono, Norio; Hara, Naoko; Shimizu, Takao; Yamada, Yuya; Kawachi, Masanori; Kiyokawa, Hiroaki; Wang, Yan Lin; Tarui, Seiichiro (1987). "Myogenic Hyperuricemia". New England Journal of Medicine. 317 (2): 75–80. doi:10.1056/NEJM198707093170203. PMID   3473284.
  34. ↑ "Harmonisation of Reference Intervals" (PDF). Pathology Harmony (UK). Archived from the original (PDF) on 2 August 2013. Retrieved 13 August 2013.
  35. ↑ Zhao, J; Huang, Y (2015). "Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy". Clinica Chimica Acta. 450: 115–20. doi:10.1016/j.cca.2015.08.005. PMID   26276048.
  36. ↑ Cirillo, P.; Sato, W.; Reungjui, S.; et al. (December 2006). "Uric acid, the metabolic syndrome, and renal disease" (PDF). Journal of the American Society of Nephrology. 17 (12 Suppl. 3): S165–S168. doi:10.1681/ASN.2006080909. PMID   17130256. S2CID   28722975.
  37. ↑ Angelopoulos, T. J.; Lowndes, J.; Zukley, L.; Melanson, K. J.; Nguyen, V.; Huffman, A.; Rippe, J. M. (June 2009). "The Effect of High-Fructose Corn Syrup Consumption on Triglycerides and Uric Acid". The Journal of Nutrition. 139 (6): 1242S–1245S. doi: 10.3945/jn.108.098194 . PMID   19403709.
  38. ↑ "High uric acid level". Mayo Clinic. 11 September 2010. Retrieved 24 April 2011.
  39. ↑ Howard, A. N. (1981). "The historical development, efficacy and safety of very-low-calorie diets". International Journal of Obesity. 5 (3): 195–208. PMID   7024153.
  40. ↑ "Diuretic-Related Side Effects: Development and Treatment". Medscape. Retrieved 17 May 2013.
  41. 1 2 3 4 Howard, S. C.; Jones, D. P.; Pui, C.-H. (12 May 2011). "The Tumor Lysis Syndrome". The New England Journal of Medicine. 364 (19): 1844–1854. doi:10.1056/NEJMra0904569. ISSN   0028-4793. PMC   3437249 . PMID   21561350.
  42. ↑ Coffee, Carole J. (1999). Quick Look Medicine: Metabolism. Hayes Barton Press. pp. 176–177. ISBN   1-59377-192-4.
  43. ↑ Li, R.; Yu, K.; Li, C. (2018). "Dietary factors and risk of gout and hyperuricemia: a meta-analysis and systematic review". Asia Pacific Journal of Clinical Nutrition. 27 (6): 1344–1356. doi:10.6133/apjcn.201811_27(6).0022. PMID   30485934.
  44. ↑ Heinig, M.; Johnson, R. J. (December 2006). "Role of uric acid in hypertension, renal disease, and metabolic syndrome". Cleveland Clinic Journal of Medicine. 73 (12): 1059–1064. doi:10.3949/ccjm.73.12.1059. PMID   17190309. S2CID   45409308.
  45. ↑ Abhishek, A; Roddy, E; Doherty, M (February 2017). "Gout - a guide for the general and acute physicians". Clinical Medicine. 17 (1): 54–59. doi:10.7861/clinmedicine.17-1-54. PMC   6297580 . PMID   28148582.
  46. ↑ Richette, P.; Bardin, T. (January 2010). "Gout". Lancet. 375 (9711): 318–328. doi:10.1016/S0140-6736(09)60883-7. PMID   19692116. S2CID   208793280.
  47. 1 2 Choi, H. K.; Atkinson, K.; Karlson, E. W.; Willett, W.; Curhan, G. (March 2004). "Purine-rich foods, dairy and protein intake, and the risk of gout in men". The New England Journal of Medicine. 350 (11): 1093–1103. doi: 10.1056/NEJMoa035700 . PMID   15014182.
  48. ↑ "Gout diet: What's allowed, what's not". Mayo Clinic . 2 July 2020.
  49. ↑ Schrauzer, Gerhard N. (2002). "Lithium: Occurrence, Dietary Intakes, Nutritional Essentiality". Journal of the American College of Nutrition. 21 (1): 14–21. doi:10.1080/07315724.2002.10719188. PMID   11838882. S2CID   25752882.
  50. ↑ "NHS Clinical Knowledge Summaries". UK National Health Service. Archived from the original on 4 March 2012.
  51. ↑ Pacher, P.; Nivorozhkin, A.; Szabó, C. (2006). "Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol". Pharmacological Reviews. 58 (1): 87–114. doi:10.1124/pr.58.1.6. PMC   2233605 . PMID   16507884.
  52. ↑ Luo, Y. C.; Do, J. S.; Liu, C. C. (October 2006). "An amperometric uric acid biosensor based on modified Ir–C electrode". Biosensors & Bioelectronics. 22 (4): 482–488. doi:10.1016/j.bios.2006.07.013. PMID   16908130.
  53. ↑ Nyhan, W. L. (March 2005). "Lesch-Nyhan Disease". Journal of the History of the Neurosciences. 14 (1): 1–10. doi:10.1080/096470490512490. PMID   15804753. S2CID   37934468.
  54. ↑ Borghi, C.; Verardi, F. M.; Pareo, I.; Bentivenga, C.; Cicero, A. F. (2014). "Hyperuricemia and cardiovascular disease risk". Expert Review of Cardiovascular Therapy. 12 (10): 1219–1225. doi:10.1586/14779072.2014.957675. PMID   25192804. S2CID   42023170.
  55. ↑ Saito, Yuichi; Tanaka, Atsushi; Node, Koichi; Kobayashi, Yoshio (July 2021). "Uric acid and cardiovascular disease: A clinical review". Journal of Cardiology. 78 (1): 51–57. doi: 10.1016/j.jjcc.2020.12.013 . ISSN   1876-4738. PMID   33388217. S2CID   230482803.
  56. ↑ Banach, K.; Bojarska, E.; Kazimierczuk, Z.; Magnowska, L.; Bzowska, A. (2005). "Kinetic Model of Oxidation Catalyzed by Xanthine Oxidase—The Final Enzyme in Degradation of Purine Nucleosides and Nucleotides". Nucleic Acids. 24 (5–7): 465–469. doi:10.1081/ncn-200060006. PMID   16247972. S2CID   42906456.
  57. ↑ Worcester, E. M.; Coe, F. L. (2008). "Nephrolithiasis". Primary Care: Clinics in Office Practice. 35 (2): 369–391. doi:10.1016/j.pop.2008.01.005. PMC   2518455 . PMID   18486720.
  58. ↑ Pak, C. Y. (September 2008). "Medical stone management: 35 years of advances". The Journal of Urology. 180 (3): 813–819. doi:10.1016/j.juro.2008.05.048. PMID   18635234.
  59. ↑ De Oliveira, E. P.; et al. (2012). "High plasma uric acid concentration: Causes and consequences". Diabetology & Metabolic Syndrome. 4: 12. doi: 10.1186/1758-5996-4-12 . PMC   3359272 . PMID   22475652.
  60. ↑ Wang, J. Y.; et al. (2012). "Predictive value of serum uric acid levels for the diagnosis of metabolic syndrome in adolescents". The Journal of Pediatrics. 161 (4): 753–6.e2. doi:10.1016/j.jpeds.2012.03.036. PMID   22575243.
  61. ↑ Hess, F. M.; King, J. C.; Margen, S. (1 December 1977). "Effect of low zinc intake and oral contraceptive agents on nitrogen utilization and clinical findings in young women". The Journal of Nutrition. 107 (12): 2219–2227. doi:10.1093/jn/107.12.2219. PMID   925768.
  62. ↑ Garg, J. P.; Chasan-Taber, S.; Blair, A.; et al. (January 2005). "Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial". Arthritis and Rheumatism. 52 (1): 290–295. doi: 10.1002/art.20781 . PMID   15641045.
  63. ↑ Wang, L.; Hu, W.; Wang, J.; Qian, W.; Xiao, H. (2016). "Low serum uric acid levels in patients with multiple sclerosis and neuromyelitis optica: An updated meta-analysis". Multiple Sclerosis and Related Disorders. 9: 17–22. doi:10.1016/j.msard.2016.05.008. PMID   27645338.
  64. ↑ Umeki, S.; Ohga, R.; Konishi, Y.; Yasuda, T.; Morimoto, K.; Terao, A. (November 1986). "Oral zinc therapy normalizes serum uric acid level in Wilson's disease patients". The American Journal of the Medical Sciences. 292 (5): 289–292. doi: 10.1097/00000441-198611000-00007 . PMID   3777013. S2CID   39995735.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.