Editing Uric acid (section)

== 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 [[mammal]]s, the enzyme [[uricase]] further oxidizes uric acid to [[allantoin]].<ref>{{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 }}</ref> The loss of uricase in higher primates parallels the similar loss of the ability to synthesize [[Vitamin C|ascorbic acid]], leading to the suggestion that urate may partially substitute for ascorbate in such species.<ref name="Proct">{{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 }}</ref> Both uric acid and ascorbic acid are strong [[reducing agent]]s ([[electron donor]]s) and potent [[antioxidant]]s. In humans, over half the antioxidant capacity of [[blood plasma]] comes from hydrogen urate ion.<ref>{{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 }}
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==== Humans ====
The normal concentration range of uric acid (or hydrogen urate ion) in human blood is 25 to 80&nbsp;mg/L for men and 15 to 60&nbsp;mg/L for women<ref>{{cite book|title=Harrison's Principles of Internal Medicine|publisher=[[McGraw-Hill Education|McGraw-Hill]]|year=1987|isbn=978-0-07-079454-2|editor-last=Braunwald|editor-first=E.|edition=11th|location=New York|page=A-3}}</ref> (but see below for slightly different values). An individual can have serum values as high as 96&nbsp;mg/L and not have gout.<ref name="hyperuricemia" /> 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]].<ref name="Vitart_2008">{{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 }}</ref> Normal excretion of uric acid in the urine is 270 to 360&nbsp;mg per day (concentration of 270 to 360&nbsp;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]].<ref>{{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 }}</ref>

=== Dogs ===
The [[Dalmatian (dog)#Kidney and bladder stones|Dalmatian]] has a genetic defect in uric acid uptake by the [[liver]] and [[kidney]]s, resulting in decreased conversion to [[allantoin]], so this breed excretes uric acid, and not allantoin, in the urine.<ref>{{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 }}</ref>

=== Birds, reptiles and desert-dwelling mammals ===
In [[bird]]s and [[reptile]]s, 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.<ref name="Hazard">{{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 }}</ref>

=== 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.<ref>{{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}}</ref>

=== 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 [[Lactic acid|lactate]] and the [[Short-chain fatty acid|short chain fatty acids]] such as  [[acetate]] and [[Butyric acid|butyrate]].<ref name="v435">{{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 }}</ref> 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.<ref name="l551">{{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}}</ref> 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".<ref name="v435" />