Uric acid 31736 223672524 2008-07-05T05:19:47Z 61.93.0.144 /* Cardiovascular disease */ {{Chembox new | Name = Uric acid | ImageFileL1 = Uric_acid.png | ImageSizeL1 = 150px | ImageFileR1 = Uric_acid3D.png | ImageSizeR1 = 120px | IUPACName = 7,9-dihydro-1H-purine-<br/>2,6,8(3H)-trione | OtherNames = 2,6,8 Trioxypurine | Section1 = {{Chembox Identifiers | EINECS = 200-720-7 | InChI = 1/C5H4N4O3/c10-3-1-2(7-4(11)6-1)8-5(12)9-3/h(H4,6,7,8,9,10,11,12)/f/h6-9H<ref>"Uric Acid." Biological Magnetic Resonance Data Bank. [http://www.bmrb.wisc.edu/metabolomics/gen_metab_summary_5.php?molName=uric_acid#INCHI Indicator Information] Retrieved on [[18 February]] [[2008]].</ref> | KEGG = C00366 | PubChem = 1175 | SMILES = C12NC(=O)NC(=O)C=2NC(=O)N1 | CASNo = 69-93-2 | RTECS = }} | Section2 = {{Chembox Properties | Formula = C<sub>5</sub>H<sub>4</sub>N<sub>4</sub>O<sub>3</sub> | MolarMass = 168g/mol | Appearance = White Crystals | Density = 1.87 | Solubility = Slightly | MeltingPt = decomposes on heating | BoilingPt = N/A | pKa = 3.89 }} }} '''Uric acid''' (or '''urate''') is an [[organic compound]] of [[carbon]], [[nitrogen]], [[oxygen]] and [[hydrogen]] with the formula C<sub>5</sub>H<sub>4</sub>N<sub>4</sub>O<sub>3</sub>. ==Metabolic processes== [[Xanthine oxidase]] oxidizes oxypurines such as [[xanthine]] and [[hypoxanthine]] to uric acid. In humans and higher primates, uric acid is the final oxidation product of [[purine metabolism|purine catabolism]]. In most other mammals, the enzyme [[uricase]] further oxidizes uric acid to [[allantoin]].<ref>[http://library.med.utah.edu/NetBiochem/pupyr/pp.htm#Pu%20Catab Purine and Pyrimidine Metabolism]</ref> The loss of uricase in higher primates parallels the similar loss of the ability to synthesize [[vitamin c|ascorbic acid]].<ref> {{cite journal | author = Proctor, P. | title = Similar Functions of Uric Acid and Ascorbate in Man | journal = Nature | year = 1970 | volume = 228 | url = http://www.ncbi.nlm.nih.gov/pubmed/5477017 | pages = 868 | doi = 10.1038/228868a0}} </ref> Both urate and ascorbate are strong [[reducing agent]]s ([[electron donor]]s) and potent [[antioxidant]]s. In humans, about half the antioxidant capacity of plasma comes from uric acid. Uric acid is also the end product of nitrogen [[catabolism]] in [[bird]]s and [[reptile]]s. In such species, it is excreted in [[feces]] as a dry mass. While this compound is produced through a complex and energetically costly [[metabolic pathway]] (in comparison to other nitrogenated wastes such as [[urea]] or [[ammonia]]), its elimination minimizes [[water]] loss. It is therefore commonly found in the excretions of animals—such as the [[kangaroo rat]]—that live in very dry environments. The [[Dalmatian]] dog has a defect in uric acid uptake by liver, resulting in decreased conversion to [[allantoin]], so this breed excretes uric acid, and not allantoin, in the urine. ==Medical issues== Humans produce large quantities of uric acid. In human [[blood]], uric acid concentrations between 3.6 mg/dL (~214µmol/L) and 8.3 mg/dL (~494µmol/L) (1mg/dL=59.48 µmol/L)<ref>[http://www.unc.edu/~rowlett/units/scales/clinical_data.html SI Units for Clinical Data]</ref> are considered normal by the [[American Medical Association]], although significantly lower levels are common in [[vegetarian]]s due to a decreased intake of [[purine]]-rich meat.<ref>{{cite journal | author = Siener R, Hesse A.| title = The effect of a vegetarian and different omnivorous diets on urinary risk factors for uric acid stone formation. | journal = Eur J Nutr | year = 2003 | volume = 42(6) | url = http://www.ncbi.nlm.nih.gov/pubmed/14673606 | pages = 332–7| doi = 10.1007/s00394-003-0428-0}}</ref> ===High uric acid=== ====Gout==== Excess serum accumulation of uric acid can lead to a type of [[arthritis]] known as [[gout]].<ref>{{cite journal | author = Tausche AK et al. | title = Hyperuricemia and gout: diagnosis and therapy. Article in German.| journal = Internist (Berl). | year = 2006 | volume = 47(5) | url = http://www.ncbi.nlm.nih.gov/pubmed/17190309 | pages = 509–20}}</ref> Elevated serum uric acid ([[hyperuricemia]]) can result from high intake of purine-rich foods, high [[fructose]] intake (regardless of fructose's low [[Glycemic Index]] (GI) value) and/or impaired excretion by the [[kidneys]]. Saturation levels of uric acid in blood may result in one form of [[kidney stone]]s when the urate crystallizes in the kidney. These uric acid stones are radiolucent and so do not appear on an abdominal x-ray. Their presence must be diagnosed by ultrasound for this reason. Some patients with gout eventually get uric [[kidney stones]]. Gout can occur where serum uric acid levels are as low as 6 mg/dL (~357µmol/L), but an individual can have serum values as high as 9.5 mg/dL (~565µmol/L) and not have gout<ref>{{cite journal | author = Laster L, Howell RR.| title = Biochemistry of uric acid and its relation to gout.| journal = N Engl J Med | year = 1963 | volume = 268 | url = http://www.ncbi.nlm.nih.gov/pubmed/16586130 | pages = 764–73}}</ref> (no abstract available; levels reported at <ref>[http://www.labcorp.com/datasets/labcorp/html/chapter/mono/pr009100.htm Uric Acid, Serum]</ref>). ====Lesch-Nyhan syndrome==== [[Lesch-Nyhan syndrome]], an extremely rare inherited disorder, is also associated with very high serum uric acid levels.<ref> {{cite journal | author = Luo YC et al.| title = An amperometric uric acid biosensor based on modified Ir-C electrode.| journal = Biosens Bioelectron | year = 2006 | volume = 22(4) | url = http://www.ncbi.nlm.nih.gov/pubmed/16908130 | pages = 482–8| doi = 10.1016/j.bios.2006.07.013}}</ref> Spasticity, involuntary movement and cognitive retardation as well as manifestations of gout are seen in cases of this syndrome.<ref>{{cite journal | author = Nyhan WL| title = Lesch-Nyhan Disease.| journal = J Hist Neurosci | year = 2005 | volume = 14(1) | url = http://www.ncbi.nlm.nih.gov/pubmed/15804753 | pages = 1–10| doi = 10.1080/096470490512490}}</ref> ====Cardiovascular disease==== Although uric acid can act as an antioxidant, excess serum accumulation is often associated with [[cardiovascular disease]]. It is not known whether this is causative (e.g., by acting as a prooxidant ) or a protective reaction taking advantage of urate's antioxidant properties. <ref>{{cite journal | author = Heinig M, Johnson RJ. | title = Role of uric acid in hypertension, renal disease, and metabolic syndrome.| journal = Cleve Clin J Med. | year = 2006 | volume = 73(12) | url = http://www.ncbi.nlm.nih.gov/pubmed/17190309 | pages = 1059–64}}</ref> ====Diabetes==== The association of high serum uric acid with insulin resistance has been known since the early part of the 20th century, nevertheless, recognition of high serum uric acid as a risk factor for diabetes has been a matter of debate. In fact, hyperuricemia has always been presumed to be a consequence of insulin resistance rather than its precursor <ref>{{cite journal | author = Cappuccio FP, et al | title = Uric acid metabolism and tubular sodium handling. Results from a population-based study. | journal = Jama | year = 1993 | volume = 270 (3) | url = http://www.ncbi.nlm.nih.gov/pubmed/8315780 | doi = 10.1001/jama.270.3.354 | pages = 354–359 | pmid = 8315780 }}</ref>. However, it was shown in a prospective follow-up study that high serum uric acid is associated with higher risk of type 2 diabetes independent of obesity, [[dyslipidemia]], and hypertension <ref> {{cite journal |author = Dehghan A. et al | title = High serum uric acid as a novel risk factor for type 2 diabetes mellitus | journal = Diabetes Care | year = 2007 | url = http://www.ncbi.nlm.nih.gov/pubmed/17977935 | doi = 10.2337/dc07-1276 | volume = 31 | pages = 361 | pmid = 17977935}}</ref>. ==== Metabolic syndrome ==== Hyperuricemia is associated with components of metabolic syndrome and it has been debated for a while to be a component of it. It has been shown in a recent study that fructose-induced hyperuricemia may play a pathogenic role in the metabolic syndrome. This agrees with the increased consumption of fructose-base drinks in recent decades and the epidemic of diabetes and obesity <ref> {{cite journal | author = Nakagawa T, Hu H, Zharikov S, et al. | title = A causal role for uric acid in fructose-induced metabolic syndrome. | journal = Am J Physiol Renal Physiol. | year = 2006 | volume = 290 (3) | url = http://www.ncbi.nlm.nih.gov/pubmed/16234313 | pages = F625–631}} </ref>. ===Low uric acid=== ====Multiple sclerosis==== Lower serum values of uric acid have been associated with [[Multiple Sclerosis]]. Multiple sclerosis (MS) patients have been found to have serum levels ~194µmol/L, with patients in relapse averaging ~160µmol/L and patients in remission averaging ~230µmol/L. Serum uric acid in healthy controls was ~290µmol/L.<ref>{{cite journal | author = Toncev G, et al. | title = Serum uric acid levels in multiple sclerosis patients correlate with activity of disease and blood-brain barrier dysfunction.| journal = Eur J Neurol. | year = 2002 | volume = 9(3) | url = http://www.ncbi.nlm.nih.gov/pubmed/11985629 | pages = 221–6 | doi = 10.1046/j.1468-1331.2002.00384.x}}</ref> Conversion factor: 1mg/dL=59.48 µmol/L<ref>[http://www.unc.edu/~rowlett/units/scales/clinical_data.html SI Units for Clinical Data]</ref> A 1998 study completed a statistical analysis of 20 million patient records, comparing serum uric acid values in patients with gout and patients with multiple sclerosis. Almost no overlap between the groups was found.<ref>{{cite journal | author = Hooper DC, et al. | title = Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. | journal = Proc Natl Acad Sci U S A. | year = 1998 | volume = 95(2) | url = http://www.ncbi.nlm.nih.gov/pubmed/9435251 | pages = 675–80 | doi = 10.1073/pnas.95.2.675 | pmid = 9435251}}</ref> Uric acid has been successfully used in the treatment and prevention of the animal (murine) model of MS. A 2006 study found that elevation of serum uric acid values in multiple sclerosis patients, by oral supplementation with [[inosine]], resulted in lower relapse rates, and no adverse effects.<ref>{{cite journal | author = Toncev G | title = Therapeutic value of serum uric acid levels increasing in the treatment of multiple sclerosis.| journal = Vojnosanit Pregl. | year = 2006 | volume = 63(10) | url = http://www.ncbi.nlm.nih.gov/pubmed/17121380 | pages = 879–82}}</ref> ===Oxidative stress=== Uric acid may be a marker of [[oxidative stress]],<ref>{{cite journal | author = Becker BF. | title = Towards the physiological function of uric acid.| journal = Free Radic Biol Med. | year = 1993 | volume = 14(6) | url = http://www.ncbi.nlm.nih.gov/pubmed/8325534 | pages = 615–31 | doi = 10.1016/0891-5849(93)90143-I}}</ref> and may have a potential therapeutic role as an [[antioxidant]] (PMID 16375736). On the other hand, like other strong reducing substances such as ascorbate, uric acid can also act as a [[prooxidant]],<ref>{{cite journal | author = Proctor P. | title = Electron-transfer factors in psychosis and dyskinesia.| journal = Physiol Chem Phys. | year = 1972 | volume = 4(4) | url = http://www.ncbi.nlm.nih.gov/pubmed/4680784 | pages = 349–60}}</ref> particularly at elevated levels. Thus, it is unclear whether elevated levels of uric acid in diseases associated with oxidative stress such as [[stroke]] and [[atherosclerosis]] are a protective response or a primary cause.<ref>[http://www.drproctor.com/crcpap2.htm Free Radicals and Human Disease]</ref> For example, some researchers propose that hyperuricemia-induced oxidative stress is a cause of [[Metabolic syndrome]].<ref>{{cite journal | author = Nakagawa T, et al | title = A causal role for uric acid in fructose-induced metabolic syndrome.| journal = Am J Physiol Renal Physiol. | year = 2006 | volume = 290(3) | url = http://www.ncbi.nlm.nih.gov/pubmed/16234313 | pages = F625–31}}</ref><ref>{{cite journal | author = Hayden MR, Tyagi SC. | title = Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle. | journal = Nutr Metab. | year = 2004 | volume = 1(1) | url = http://www.ncbi.nlm.nih.gov/pubmed/15507132 | pages = 10 | doi = 10.1186/1743-7075-1-10}}</ref> On the other hand, plasma uric acid levels correlate with longevity in primates and other mammals.<ref>{{cite journal | author = Cutler RG. | title = Urate and ascorbate: their possible roles as antioxidants in determining longevity of mammalian species. | journal = Arch Gerontol Geriatr. | year = 1984 | volume = 3(4) | url = http://www.ncbi.nlm.nih.gov/pubmed/6532339 | pages = 321–48 | doi = 10.1016/0167-4943(84)90033-5}}</ref> This is presumably a function of urate's antioxidant properties. ==Sources of uric acid== In many instances, people have elevated uric acid levels for hereditary reasons. Diet may also be a factor. Purines are found in high amounts in animal food products, especially internal organs.<ref>[http://www.dietaryfiberfood.com/purine-food.php Gout Causes: List of Diet/Food Sources High or Low in Purine Content]</ref> Examples of high purine sources include: sweetbreads, anchovies, sardines, liver, beef kidneys, brains, meat extracts (e.g Oxo, Bovril), herring, mackerel, scallops, game meats, and gravy. A moderate amount of purine is also contained in beef, pork, poultry, fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran and wheat germ.<ref>[http://www.healthcastle.com/gout.shtml Gout Diet / Low Purine Diet - Limit High Purine foods]</ref> Moderate intake of purine-containing food is not associated with an increased risk of gout.<ref>{{cite journal | author = Choi HK, et al. | title = Purine-rich foods, dairy and protein intake, and the risk of gout in men. | journal = N Engl J Med. | year = 2004 | volume = 350(11) | url = http://www.ncbi.nlm.nih.gov/pubmed/15014182 | pages = 1093–103 | doi = 10.1056/NEJMoa035700 | pmid = 15014182}}</ref> Serum uric acid can be elevated due to high [[fructose]] intake <ref>{{cite journal | author = Nakagawa T, et al | title = A causal role for uric acid in fructose-induced metabolic syndrome.| journal = Am J Physiol Renal Physiol. | year = 2006 | volume = 290(3) | url = http://www.ncbi.nlm.nih.gov/pubmed/16234313 | pages = F625–31}}</ref>, reduced excretion by the kidneys, and or high intake of dietary purine. Fructose can be found in processed foods and soda beverages - in some countries, in the form of [[high fructose corn syrup]]. ==Causes of low uric acid== Aside from avoidance of purine foods, both accumulated copper and low vitamin B2 can exacerbate low uric acid levels, which in turn is hypothesized to lead to myelin degeneration seen in multiple sclerosis.<ref>{{cite journal | author = Johnson S. | title = The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis. | journal = Med Hypotheses. | year = 2000 | volume = 55(3) | url = http://www.ncbi.nlm.nih.gov/pubmed/10985916 | pages = 239–41 | doi = 10.1054/mehy.2000.1051}}</ref> ==Other uric acid facts== The high nitrogen content of uric acid makes [[guano]] a useful agricultural [[fertilizer]]. The crystalline form of uric acid is used as a reflector in certain species of [[firefly|fireflies]]. The uric acid in urine can also dry in a baby's diaper to form a pinkish powder that is harmless. ==See also== * [[Hyperuricemia]] ==References== <references/> ==External links== * [http://www.nlm.nih.gov/medlineplus/ency/article/003476.htm MedlinePlus] - Uric Acid Test * [http://www.iksi.org International Kidney Stone Institute] * [http://www.dietaryfiberfood.com/purine-food.php Purine content in food] * [http://www.compchemwiki.org/index.php?title=Uric_acid Computational Chemistry Wiki] [[Category:Uric acid| ]] [[Category:Nitrogen heterocycles]] [[Category:Nitrogen metabolism]] [[Category:Organic acids]] [[cs:Kyselina močová]] [[da:Urinsyre]] [[de:Harnsäure]] [[es:Ácido úrico]] [[fr:Acide urique]] [[it:Acido urico]] [[he:חומצת שתן]] [[mk:Мочна киселина]] [[nl:Urinezuur]] [[ja:尿酸]] [[pl:Kwas moczowy]] [[pt:Ácido úrico]] [[ru:Мочевая кислота]] [[sv:Urinsyra]] [[th:กรดยูริก]] [[tr:Ürik asit]] [[zh:尿酸]]