Uric acid#Gout

Uric acid was first isolated from kidney stones in 1776 by Swedish chemist Carl Wilhelm Scheele.{{cite journal|author-link=Carl Wilhelm Scheele|last=Scheele|first=C. W.|title=Examen Chemicum Calculi Urinari|trans-title=A chemical examiniation of kidney stones|journal=Opuscula|date=1776|volume=2|page=73}} In 1882, the Ukrainian chemist Ivan Horbaczewski first synthesized uric acid by melting urea with glycine.{{cite journal|first=J.|last=Horbaczewski|date=1882|url=https://books.google.com/books?id=b448AAAAIAAJ&pg=PA796|title=Synthese der Harnsäure|trans-title=Synthesis of uric acid|journal=Monatshefte für Chemie und Verwandte Teile Anderer Wissenschaften|volume=3|pages=796–797|doi=10.1007/BF01516847|s2cid=92323943}}

Uric acid displays lactam–lactim tautomerism.{{cite book|last1=Lieberman|first1=M.|url=https://archive.org/details/marksessentialme0000lieb|title=Marks' Essential Medical Biochemistry|last2=Marks|first2=A. D.|last3=Smith|first3=C. M.|last4=Marks|first4=D. B.|publisher=Lippincott Williams & Wilkins|year=2007|isbn=978-0-7817-9340-7|location=Philadelphia|pages=[https://archive.org/details/marksessentialme0000lieb/page/47 47]–|url-access=registration}} Uric acid crystallizes in the lactam form,{{cite journal |last1=Ringertz |first1=H. |title=The molecular and crystal structure of uric acid |journal=Acta Crystallographica |date=1 March 1966 |volume=20 |issue=3 |pages=397–403 |doi=10.1107/S0365110X66000914|doi-access=free |bibcode=1966AcCry..20..397R }} with computational chemistry also indicating that tautomer to be the most stable.{{cite journal |last1=Jiménez |first1=V. |last2=Alderete |first2=J. B. |title=Theoretical calculations on the tautomerism of uric acid in gas phase and aqueous solution |journal=Journal of Molecular Structure: THEOCHEM |date=November 2005 |volume=755 |issue=1–3 |pages=209–214 |doi=10.1016/j.theochem.2005.08.001}} Uric acid is a diprotic acid with pK_a1 = 5.4 and pK_a2 = 10.3.{{cite book|last=McCrudden|first=F. H.|title=Uric Acid: The Chemistry, Physiology and Pathology of Uric Acid and the Physiologically Important Purin Bodies, with a Discussion of the Metabolism in Gout|publisher=BiblioBazaar|year=2008|isbn=978-0-554-61991-0|location=Charleston, SC|orig-year=1905}} At physiological pH, urate predominates in solution.{{medical citation needed|date=August 2024}}

File:Harnsäure Ketoform.svg

File:Urat.svg

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.{{Cite journal |first1=K. |last1=Ichida |first2=Y. |last2=Amaya |first3=K. |last3=Noda |first4=S. |last4=Minoshima |first5=T. |last5=Hosoya |first6=O. |last6=Sakai |first7=N. |last7=Shimizu |first8=T. |last8=Nishino |date=November 1993 |title=Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): Structural analysis of the protein and chromosomal location of the gene |url=https://linkinghub.elsevier.com/retrieve/pii/037811199390652J |journal=Gene |language=en |volume=133 |issue=2 |pages=279–284 |doi=10.1016/0378-1119(93)90652-J |pmid=8224915 |access-date=1 January 2022 |archive-date=15 June 2022 |archive-url=https://web.archive.org/web/20220615142523/https://linkinghub.elsevier.com/retrieve/pii/037811199390652J |url-status=live |url-access=subscription }} 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.{{cite journal | pmid = 15581570 | year = 2005 | last1 = Hille | first1 = R. | title = Molybdenum-containing hydroxylases | volume = 433 | issue = 1 | pages = 107–116 | doi = 10.1016/j.abb.2004.08.012 | journal = Archives of Biochemistry and Biophysics}} Uric acid is released in hypoxic conditions (low oxygen saturation).{{Cite journal| volume = 131| issue = 5| pages = 1473–1478| last1 = Baillie| first1 = J. K. |first2=M. G. |last2=Bates |first3=A. A. |last3=Thompson |first4=W. S. |last4=Waring |first5=R. W. |last5=Partridge |first6=M. F. |last6=Schnopp |first7=A. |last7=Simpson |first8=F. |last8=Gulliver-Sloan |first9=S. R. |last9=Maxwell |first10=D. J. |last10=Webb | title = Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude| journal = Chest| date = May 2007| doi = 10.1378/chest.06-2235| pmid = 17494796}}

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|date=August 2024}}

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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.{{cite book|title=CRC Handbook of Chemistry and Physics|title-link=CRC Handbook of Chemistry and Physics|publisher=CRC Press|year=1981|editor-last=Weast|editor-first=R. C.|edition=62nd|location=Boca Raton, FL|oclc=7842683}}{{cite book|title=Merck Index|publisher=Merck|year=1976|isbn=978-0-911910-26-1|editor-last=Windholz|editor-first=M.|edition=9th}}{{cite book | title = Uric acid | first = Francis H. | last = McCrudden | page = 58}}

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.{{cite web |last=Angstadt |first=C. N. |title=Purine and Pyrimidine Metabolism: Purine Catabolism |website=NetBiochem |date=4 December 1997 |url=http://library.med.utah.edu/NetBiochem/pupyr/pp.htm#Pu%20Catab |access-date=28 December 2006 |archive-date=27 November 2020 |archive-url=https://web.archive.org/web/20201127012354/http://library.med.utah.edu/NetBiochem/pupyr/pp.htm#Pu%20Catab |url-status=live }} 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.{{cite journal |last=Proctor |first=P. |title=Similar functions of uric acid and ascorbate in man? |journal=Nature |volume=228 |issue=5274 |pages=868 |date=November 1970 |pmid=5477017 |doi= 10.1038/228868a0|bibcode=1970Natur.228..868P |s2cid=4146946 |doi-access=free }} 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.{{cite journal | doi = 10.1046/j.1365-2362.1997.1390687.x | title = Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus | year = 1997 | last1 = Maxwell | first1 = S. R. J. | last2 = Thomason | first2 = H. | last3 = Sandler | first3 = D. | last4 = Leguen | first4 = C. | last5 = Baxter | first5 = M. A. | last6 = Thorpe | first6 = G. H. G. | last7 = Jones | first7 = A. F. | last8 = Barnett | first8 = A. H. | journal = European Journal of Clinical Investigation | volume = 27 | issue = 6 | pages = 484–490 | pmid = 9229228| s2cid = 11773699 }}

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{{cite book|title=Harrison's Principles of Internal Medicine|publisher=McGraw-Hill|year=1987|isbn=978-0-07-079454-2|editor-last=Braunwald|editor-first=E.|edition=11th|location=New York|page=A-3}} (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.{{cite journal |last1=Vitart |first1=V. |last2=Rudan |first2=I. |last3=Hayward |first3=C. |display-authors=etal |title=SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout |journal=Nature Genetics |volume=40 |issue=4 |pages=437–442 |date=April 2008 |pmid=18327257 |doi=10.1038/ng.106 |s2cid=6720464 }} 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.{{Cite book | url=https://www.ncbi.nlm.nih.gov/books/NBK562201/ | pmid=32965872 | title=StatPearls | chapter=Hyperuricosuria | year=2022 | publisher=StatPearls | last1=Kaur | first1=P. | last2=Bhatt | first2=H. | access-date=21 March 2022 | archive-date=26 October 2022 | archive-url=https://web.archive.org/web/20221026085112/https://www.ncbi.nlm.nih.gov/books/NBK562201/ | url-status=live }}

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.{{cite journal |last1=Friedman |first1=M. |last2=Byers |first2=S. O. |name-list-style=amp |title=Observations concerning the causes of the excess excretion of uric acid in the Dalmatian dog |journal=The Journal of Biological Chemistry |volume=175 |issue=2 |pages=727–735 |date=1 September 1948 |doi=10.1016/S0021-9258(18)57191-X |pmid=18880769 |doi-access=free }}

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.{{cite book | last = Hazard | first = L. C. | title = Sodium and Potassium Secretion by Iguana Salt Glands | series = Iguanas: Biology and Conservation | publisher = University of California Press | pages = 84–85 | year = 2004 | isbn = 978-0-520-23854-1 | url = https://books.google.com/books?id=Dyb8bNBh5nwC }}

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.{{cite journal|last1=Zeeck|first1=E.|last2=Harder|first2=T.|last3=Beckmann|first3=M.|title= Uric acid: the sperm-release pheromone of the marine polychaete Platynereis dumerilii |journal=Journal of Chemical Ecology|date=1998|volume=24|issue=1|pages=13–22|doi=10.1023/A:1022328610423|bibcode=1998JCEco..24...13Z |s2cid=42318049}}

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.{{cite journal |last1=Liu |first1=Yuanyuan |last2=Jarman |first2=J. Bryce |last3=Low |first3=Yen S. |last4=Augustijn |first4=Hannah E. |last5=Huang |first5=Steven |last6=Chen |first6=Haoqing |last7=DeFeo |first7=Mary E. |last8=Sekiba |first8=Kazuma |last9=Hou |first9=Bi-Huei |last10=Meng |first10=Xiandong |last11=Weakley |first11=Allison M. |last12=Cabrera |first12=Ashley V. |last13=Zhou |first13=Zhiwei |last14=van Wezel |first14=Gilles |last15=Medema |first15=Marnix H. |year=2023 |title=A widely distributed gene cluster compensates for uricase loss in hominids |journal=Cell |volume=186 |issue=16 |pages=3400–3413.e20 |doi=10.1016/j.cell.2023.06.010 |issn=0092-8674 |doi-access=free |last16=Ganesan |first16=Calyani |last17=Pao |first17=Alan C. |last18=Gombar |first18=Saurabh |last19=Dodd |first19=Dylan|pmid=37541197 |pmc=10421625 |hdl=1887/3719494 |hdl-access=free }} 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.{{cite journal |last=Sorensen |first=Leif B. |year=1965 |title=Role of the intestinal tract in the elimination of uric acid |journal=Arthritis & Rheumatism |publisher=Wiley |volume=8 |issue=4 |pages=694–706 |doi=10.1002/art.1780080429 |pmid=5859543 |issn=0004-3591}} 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".

Although foods such as meat and seafood can elevate serum urate levels, genetic variation is a much greater contributor to high serum urate.{{cite journal | last1=Major |first1=T. J. |last2=Topless |first2=R. K. |last3=Merriman |first3=T. R. | title=Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts | journal=The BMJ | volume=363 | pages=k3951 | year=2018 | doi = 10.1136/bmj.k3951 | pmc=6174725 | pmid=30305269}}{{cite journal | author=Keenan |first=R. T. | title=The biology of urate | journal=Seminars in Arthritis and Rheumatism | volume=50 | issue=35| pages=S2–S10 | year=2020 | doi = 10.1016/j.semarthrit.2020.04.007 | pmid=32620198 |doi-access=free }} 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.{{cite journal |last1=Aringer |first1=M. |last2=Graessler |first2=J. |title=Understanding deficient elimination of uric acid |journal=Lancet |volume=372 |issue=9654 |pages=1929–1930 |date=December 2008 |pmid=18834627 |doi=10.1016/S0140-6736(08)61344-6|s2cid=1839089 }}{{cite journal |last1=Kolz |first1=M. |last2=Johnson |first2=T. |display-authors=etal | editor1-last=Allison | editor1-first=David B. |title=Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations | journal=PLOS Genet. |date=June 2009 | volume=5 | issue=6 | pmid=19503597 | doi=10.1371/journal.pgen.1000504 | pages=e1000504 | pmc=2683940 |doi-access=free }}{{cite journal|last=Köttgen|first=A.|title=Genome-wide association analyses identify 18 new loci associated with serum urate concentrations|journal=Nature Genetics|date=February 2013|volume=45|issue=2|pages=145–154|pmid=23263486|doi=10.1038/ng.2500|pmc=3663712|display-authors=etal|url=https://www.pure.ed.ac.uk/ws/files/8739767/Genome_wide_association_analyses_identify_18_new_loci_associated_with_serum_urate_concentrations.pdf}} GLUT9, encoded by the SLC2A9 gene, is known to transport both uric acid and fructose.{{cite journal |last1=Döring |first1=A. |last2=Gieger |first2=C. |last3=Mehta |first3=D. |display-authors=etal |title=SLC2A9 influences uric acid concentrations with pronounced sex-specific effects |journal=Nature Genetics |volume=40 |issue=4 |pages=430–436 |date=April 2008 |pmid=18327256 |doi=10.1038/ng.107|s2cid=29751482 }}{{Cite journal|last1=Mandal|first1=Asim K.|last2=Mount|first2=David B.|date=February 2015|title=The molecular physiology of uric acid homeostasis|url=https://pubmed.ncbi.nlm.nih.gov/25422986/|journal=Annual Review of Physiology|volume=77|pages=323–345|doi=10.1146/annurev-physiol-021113-170343|pmid=25422986}}

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.{{cite journal | doi=10.1056/NEJM198707093170203 | title=Myogenic Hyperuricemia | year=1987 | last1=Mineo | first1=Ikuo | last2=Kono | first2=Norio | last3=Hara | first3=Naoko | last4=Shimizu | first4=Takao | last5=Yamada | first5=Yuya | last6=Kawachi | first6=Masanori | last7=Kiyokawa | first7=Hiroaki | last8=Wang | first8=Yan Lin | last9=Tarui | first9=Seiichiro | journal=New England Journal of Medicine | volume=317 | issue=2 | pages=75–80 | pmid=3473284 }} 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. Excess AMP (adenosine monophosphate) is converted into uric acid.

AMP → IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid

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).{{cite web|title=Harmonisation of Reference Intervals|url=http://www.acb.org.uk/docs/Pathology%20Harmony%20for%20web.pdf|website=Pathology Harmony (UK)|access-date=13 August 2013|url-status=dead|archive-url=https://web.archive.org/web/20130802082027/http://www.acb.org.uk/docs/Pathology%20Harmony%20for%20web.pdf|archive-date=2 August 2013}} 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.{{Cite journal|pmid=26276048|year=2015|last1=Zhao|first1=J|title=Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy|journal=Clinica Chimica Acta|volume=450|pages=115–20|last2=Huang|first2=Y|doi=10.1016/j.cca.2015.08.005}}

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

• Diet may be a factor. High intake of dietary purine, high-fructose corn syrup, and sucrose can increase levels of uric acid.{{cite journal |pmid=17130256 |doi=10.1681/ASN.2006080909 |volume=17 |issue=12 Suppl. 3 |title=Uric acid, the metabolic syndrome, and renal disease |date=December 2006 |last1=Cirillo |first1=P. |last2=Sato |first2=W. |last3=Reungjui |first3=S. |display-authors=etal |journal=Journal of the American Society of Nephrology |pages=S165–S168 |s2cid=28722975 |url=http://jasn.asnjournals.org/content/17/12_suppl_3/S165.full.pdf |access-date=20 April 2018 |archive-date=15 May 2013 |archive-url=https://web.archive.org/web/20130515003345/http://jasn.asnjournals.org/content/17/12_suppl_3/S165.full.pdf |url-status=live }}{{cite journal | pmid = 19403709 | doi=10.3945/jn.108.098194 | volume=139 | issue=6 | title=The Effect of High-Fructose Corn Syrup Consumption on Triglycerides and Uric Acid |date=June 2009 | first1=T. J. |last1=Angelopoulos |first2=J. |last2=Lowndes |first3=L. |last3=Zukley |first4=K. J. |last4=Melanson |first5=V. |last5=Nguyen |first6=A. |last6=Huffman |first7=J. M. |last7=Rippe | journal=The Journal of Nutrition | pages=1242S–1245S|doi-access=free }}
• Serum uric acid can be elevated by reduced excretion via the kidneys.{{cite web |date=11 September 2010 |url=http://www.mayoclinic.com/health/high-uric-acid-level/MY00160 |title=High uric acid level |website=Mayo Clinic |access-date=24 April 2011 |archive-date=25 August 2011 |archive-url=https://web.archive.org/web/20110825234358/http://www.mayoclinic.com/health/high-uric-acid-level/MY00160 |url-status=live }}
• Fasting or rapid weight loss can temporarily elevate uric acid levels.{{cite journal| last = Howard | first = A. N. | title = The historical development, efficacy and safety of very-low-calorie diets| journal = International Journal of Obesity| volume = 5| issue = 3| pages = 195–208| year = 1981| pmid = 7024153}}
• Certain drugs, such as thiazide diuretics, can increase blood uric acid levels by interfering with renal clearance.{{cite web|title=Diuretic-Related Side Effects: Development and Treatment|work=Medscape |url=http://www.medscape.com/viewarticle/489521_7|access-date=17 May 2013|archive-date=4 May 2013|archive-url=https://web.archive.org/web/20130504004901/http://www.medscape.com/viewarticle/489521_7|url-status=live}}
• Tumor lysis syndrome, a metabolic complication of certain cancers or chemotherapy, due to nucleobase and potassium release into the plasma.
• Pseudohypoxia (disrupted NADH/NAD⁺ ratio) caused by diabetic hyperglycemia and excessive alcohol consumption.{{Cite book |last=Coffee |first=Carole J. |title=Quick Look Medicine: Metabolism |publisher=Hayes Barton Press |year=1999 |isbn=1-59377-192-4 |pages=176–177}}

{{main|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.{{cite journal | last1=Li |first1=R. |last2=Yu |first2=K. |last3=Li |first3=C. | title=Dietary factors and risk of gout and hyperuricemia: a meta-analysis and systematic review | journal=Asia Pacific Journal of Clinical Nutrition | volume=27 | issue=6 | pages=1344–1356 | year=2018 | doi = 10.6133/apjcn.201811_27(6).0022 | pmid=30485934}}

Excess blood uric acid (serum urate) can induce gout,{{cite journal |last1=Heinig |first1=M. |last2=Johnson |first2=R. J. |title=Role of uric acid in hypertension, renal disease, and metabolic syndrome |journal=Cleveland Clinic Journal of Medicine |volume=73 |issue=12 |pages=1059–1064 |date=December 2006 |pmid=17190309 |doi=10.3949/ccjm.73.12.1059|doi-broken-date=29 November 2024 |s2cid=45409308 }} a painful condition resulting from needle-like crystals of uric acid termed monosodium urate crystals{{cite journal |last1=Abhishek |first1=A |last2=Roddy |first2=E |last3=Doherty |first3=M |title=Gout - a guide for the general and acute physicians. |journal=Clinical Medicine |date=February 2017 |volume=17 |issue=1 |pages=54–59 |doi=10.7861/clinmedicine.17-1-54 |pmid=28148582|pmc=6297580 }} precipitating in joints, capillaries, skin, and other tissues.{{cite journal |last1=Richette |first1=P. |last2=Bardin |first2=T. |title=Gout |journal=Lancet |volume=375 |issue=9711 |pages=318–328 |date=January 2010 |pmid=19692116 |doi=10.1016/S0140-6736(09)60883-7 |s2cid=208793280 }} 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.{{cite journal |last1=Tausche |first1=A. K. |last2=Unger |first2=S. |last3=Richter |first3=K. |display-authors=etal |trans-title=Hyperuricemia and gout: diagnosis and therapy |language=de |journal=Der Internist |volume=47 |issue=5 |pages=509–521 |date=May 2006 |pmid=16586130 |doi=10.1007/s00108-006-1578-y |title=Hyperurikämie und Gicht|s2cid=11480796 }}

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.{{cite journal |last1=Choi |first1=H. K. |last2=Atkinson |first2=K. |last3=Karlson |first3=E. W. |last4=Willett |first4=W. |last5=Curhan |first5=G. |title=Purine-rich foods, dairy and protein intake, and the risk of gout in men |journal=The New England Journal of Medicine |volume=350 |issue=11 |pages=1093–1103 |date=March 2004 |pmid=15014182 |doi=10.1056/NEJMoa035700|doi-access=free }} Purine-rich foods include liver, kidney, and sweetbreads, and certain types of seafood, including anchovies, herring, sardines, mussels, scallops, trout, haddock, mackerel, and tuna.{{Cite web|date=July 2, 2020|title=Gout diet: What's allowed, what's not|url=http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/gout-diet/art-20048524|website=Mayo Clinic|publisher=|access-date=13 January 2017|archive-date=7 January 2017|archive-url=https://web.archive.org/web/20170107022952/http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/gout-diet/art-20048524|url-status=live}} Moderate intake of purine-rich vegetables, however, is not associated with an increased risk of gout.

One treatment for gout in the 19th century was administration of lithium salts;{{cite journal |first= Gerhard N. |last=Schrauzer |journal=Journal of the American College of Nutrition |volume=21 |issue=1 |pages=14–21 |year=2002 |title= Lithium: Occurrence, Dietary Intakes, Nutritional Essentiality |pmid= 11838882 |doi= 10.1080/07315724.2002.10719188|s2cid=25752882 }} 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.{{cite web|title=NHS Clinical Knowledge Summaries |url=http://www.cks.nhs.uk/gout/background_information/causes_and_risk_factors#-291124 |url-status=dead |archive-url=https://web.archive.org/web/20120304060453/http://www.cks.nhs.uk/gout/background_information/causes_and_risk_factors |archive-date=4 March 2012 |publisher=UK National Health Service}} Allopurinol, which weakly inhibits xanthine oxidase, is an analog of hypoxanthine that is hydroxylated by xanthine oxidoreductase at the 2-position to give oxipurinol.{{cite journal|pmid=16507884|pmc=2233605|year=2006|last1=Pacher|first1=P.|title=Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol|journal=Pharmacological Reviews|volume=58|issue=1|pages=87–114|last2=Nivorozhkin|first2=A.|last3=Szabó|first3=C.|doi=10.1124/pr.58.1.6}}

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.{{Cite journal|last1=Howard|first1=S. C.|last2=Jones|first2=D. P.|last3=Pui|first3=C.-H.|date=12 May 2011|title=The Tumor Lysis Syndrome|journal=The New England Journal of Medicine|volume=364|issue=19|pages=1844–1854|doi=10.1056/NEJMra0904569|issn=0028-4793|pmc=3437249|pmid=21561350}} Tumor lysis syndrome may lead to acute kidney injury when uric acid crystals are deposited in the kidneys. 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.

Lesch–Nyhan syndrome, a rare inherited disorder, is also associated with high serum uric acid levels.{{cite journal |last1=Luo |first1=Y. C. |last2=Do |first2=J. S. |last3=Liu |first3=C. C. |title=An amperometric uric acid biosensor based on modified Ir–C electrode |journal=Biosensors & Bioelectronics |volume=22 |issue=4 |pages=482–488 |date=October 2006 |pmid=16908130 |doi=10.1016/j.bios.2006.07.013}} Spasticity, involuntary movement, and cognitive retardation as well as manifestations of gout are seen in this syndrome.{{cite journal |last=Nyhan |first=W. L. |title=Lesch-Nyhan Disease |journal=Journal of the History of the Neurosciences |volume=14 |issue=1 |pages=1–10 |date=March 2005 |pmid=15804753 |doi=10.1080/096470490512490|s2cid=37934468 }}

Hyperuricemia is associated with an increase in risk factors for cardiovascular disease.{{cite journal|journal=Expert Review of Cardiovascular Therapy |year=2014 |volume=12 |issue=10 |pages=1219–1225 |doi=10.1586/14779072.2014.957675 |pmid=25192804|title=Hyperuricemia and cardiovascular disease risk |last1=Borghi |first1=C. |last2=Verardi |first2=F. M. |last3=Pareo |first3=I. |last4=Bentivenga |first4=C. |last5=Cicero |first5=A. F.|s2cid=42023170 }} 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.{{Cite journal |last1=Saito |first1=Yuichi |last2=Tanaka |first2=Atsushi |last3=Node |first3=Koichi |last4=Kobayashi |first4=Yoshio |date=July 2021 |title=Uric acid and cardiovascular disease: A clinical review |journal=Journal of Cardiology |volume=78 |issue=1 |pages=51–57 |doi=10.1016/j.jjcc.2020.12.013 |issn=1876-4738 |pmid=33388217|s2cid=230482803 |doi-access=free }}

File:Urine crystals comparison.png

Kidney stones can form through deposits of sodium urate microcrystals.{{cite journal |last1=Banach |first1=K. |last2=Bojarska |first2=E. |last3=Kazimierczuk |first3=Z. |last4=Magnowska |first4=L. |last5=Bzowska |first5=A. |date=2005 |title=Kinetic Model of Oxidation Catalyzed by Xanthine Oxidase—The Final Enzyme in Degradation of Purine Nucleosides and Nucleotides |journal=Nucleic Acids |volume=24 |issue=5–7 |pages=465–469 |doi=10.1081/ncn-200060006 |pmid=16247972 |s2cid=42906456}}

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.{{Cite journal |last1=Worcester |first1=E. M. |last2=Coe |first2=F. L. |date=2008 |title=Nephrolithiasis |journal=Primary Care: Clinics in Office Practice |language=en |volume=35 |issue=2 |pages=369–391 |doi=10.1016/j.pop.2008.01.005 |pmc=2518455 |pmid=18486720}} Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seed crystals".{{cite journal |last=Pak |first=C. Y. |date=September 2008 |title=Medical stone management: 35 years of advances |journal=The Journal of Urology |volume=180 |issue=3 |pages=813–819 |doi=10.1016/j.juro.2008.05.048 |pmid=18635234}}

Hyperuricemia is associated with components of metabolic syndrome, including in children.{{Cite journal|last=De Oliveira|first=E. P. |display-authors=etal |date=2012|title=High plasma uric acid concentration: Causes and consequences|journal=Diabetology & Metabolic Syndrome|volume=4|pages=12|pmid=22475652|pmc=3359272|doi=10.1186/1758-5996-4-12 |doi-access=free }}{{Cite journal|last=Wang|first=J. Y.|display-authors=etal|date=2012|title=Predictive value of serum uric acid levels for the diagnosis of metabolic syndrome in adolescents|journal=The Journal of Pediatrics|volume=161 |issue=4|pages=753–6.e2|pmid=22575243|doi=10.1016/j.jpeds.2012.03.036}}

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.{{cite journal |last1=Hess |first1=F. M. |last2=King |first2=J. C. |last3=Margen |first3=S. |title=Effect of low zinc intake and oral contraceptive agents on nitrogen utilization and clinical findings in young women |journal=The Journal of Nutrition |volume=107 |issue=12 |pages=2219–2227 |date=1 December 1977|pmid=925768 |doi=10.1093/jn/107.12.2219}} Sevelamer, a drug indicated for prevention of hyperphosphataemia in people with chronic kidney failure, can significantly reduce serum uric acid.{{cite journal |last1=Garg |first1=J. P. |last2=Chasan-Taber |first2=S. |last3=Blair |first3=A. |display-authors=etal |title=Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial |journal=Arthritis and Rheumatism |volume=52 |issue=1 |pages=290–295 |date=January 2005 |pmid=15641045 |doi=10.1002/art.20781|doi-access=free }}

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.{{cite journal |last1=Wang |first1=L. |last2=Hu |first2=W. |last3=Wang |first3=J. |last4=Qian |first4=W. |last5=Xiao |first5=H. |year=2016 |title=Low serum uric acid levels in patients with multiple sclerosis and neuromyelitis optica: An updated meta-analysis |pmid=27645338 |journal=Multiple Sclerosis and Related Disorders |volume=9 |pages=17–22 |doi=10.1016/j.msard.2016.05.008}}

Correcting low or deficient zinc levels can help elevate serum uric acid.{{cite journal |last1=Umeki |first1=S. |last2=Ohga |first2=R. |last3=Konishi |first3=Y. |last4=Yasuda |first4=T. |last5=Morimoto |first5=K. |last6=Terao |first6=A. |title=Oral zinc therapy normalizes serum uric acid level in Wilson's disease patients |journal=The American Journal of the Medical Sciences |volume=292 |issue=5 |pages=289–292 |date=November 1986 |pmid=3777013 |doi=10.1097/00000441-198611000-00007|s2cid=39995735 |doi-access=free }}

• 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

{{Reflist|30em}}

{{Commons category}}

• [https://www.nlm.nih.gov/medlineplus/ency/article/003476.htm Uric acid blood test – MedlinePlus]

{{Nucleotide metabolism intermediates}}

{{Antioxidants}}

{{Purinergics}}

{{Authority control}}

{{DEFAULTSORT:Uric Acid}}

Category:Nitrogen cycle

Category:Organic acids