Uric acid

chembox
Name = Uric acid
ImageFileL1 = Uric_acid.png ImageSizeL1 = 150px
ImageFileR1 = Uric_acid3D.png ImageSizeR1 = 120px
IUPACName = 7,9-dihydro-1H-purine- 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 ["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.]
KEGG = C00366
PubChem = 1175
SMILES = C12NC(=O)NC(=O)C=2NC(=O)N1
CASNo = 69-93-2
ChemSpiderID = 1142
RTECS =
Section2 = Chembox Properties
Formula = C₅H₄N₄O₃
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 C₅H₄N₄O₃.

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 catabolism. In most other mammals, the enzyme uricase further oxidizes uric acid to allantoin. [ [http://library.med.utah.edu/NetBiochem/pupyr/pp.htm#Pu%20Catab Purine and Pyrimidine Metabolism] ] The loss of uricase in higher primates parallels the similar loss of the ability to synthesize ascorbic acid. [ 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 ] Both urate and ascorbate are strong reducing agents (electron donors) and potent antioxidants. In humans, over half the antioxidant capacity of plasma comes from uric acid.

Uric acid is also the end product of nitrogen catabolism in birds and reptiles. 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) [ [http://www.unc.edu/~rowlett/units/scales/clinical_data.html SI Units for Clinical Data] ] are considered normal by the American Medical Association, although significantly lower levels are common in vegetarians due to a decreased intake of purine-rich meat. [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]

High uric acid

Gout

Excess serum accumulation of uric acid can lead to a type of arthritis known as gout. [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 | doi = 10.1007/s00108-006-1578-y]

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 stones 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 [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] (no abstract available; levels reported at [ [http://www.labcorp.com/datasets/labcorp/html/chapter/mono/pr009100.htm Uric Acid, Serum] ] ).

Lesch-Nyhan syndrome

Lesch-Nyhan syndrome, an extremely rare inherited disorder, is also associated with very high serum uric acid levels. [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]

Spasticity, involuntary movement and cognitive retardation as well as manifestations of gout are seen in cases of this syndrome. [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]

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. [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]

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 [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 ] . 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 [ 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] .

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 [ 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 ] .

Uric Acid Stone Formation

Uric acid stones, which form in the absence of secondary causes such as chronic diarrhea, vigorous exercise, dehydration, and animal protein loading, are felt to be secondary to obesity and insulin resistance seen in metabolic syndrome. Increased dietary acid leads to increased endogenous acid production in the liver and muscles which in turn leads to an increased acid load to the kidneys. This load is handled more poorly because of renal fat infiltration and insulin resistance which are felt to impair ammonia excretion (a buffer). The urine is therefore quite acidic and uric acid becomes insoluble, crystallizes and stones form. In addition, naturally present promoter and inhibitor factors may be affected. This explains the the high prevalence of uric stones and unusually acid urine seen in patients with Type II diabetes. Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seed crystals" (heterogenous nucleation). [ cite journal | author = Charles Y.C. Pak | title = Metabolic Stone Management: 35 Years of Advances. | journal = Journal of Urology | year = 2008 | volume = 180 pages = 813-819 ]

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. [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] Conversion factor: 1mg/dL=59.48 µmol/L [ [http://www.unc.edu/~rowlett/units/scales/clinical_data.html SI Units for Clinical Data] ]

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. [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]

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. [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]

Oxidative stress

Uric acid may be a marker of oxidative stress, [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] 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, [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] 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. [ [http://www.drproctor.com/crcpap2.htm Free Radicals and Human Disease] ]

For example, some researchers propose that hyperuricemia-induced oxidative stress is a cause of Metabolic syndrome. [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] [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] On the other hand, plasma uric acid levels correlate with longevity in primates and other mammals. [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] This is presumably a function of urate's antioxidant properties.

ources 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. [ [http://www.dietaryfiberfood.com/purine-food.php Gout Causes: List of Diet/Food Sources High or Low in Purine Content] ]

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. [ [http://www.healthcastle.com/gout.shtml Gout Diet / Low Purine Diet - Limit High Purine foods] ]

Moderate intake of purine-containing food is not associated with an increased risk of gout. [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]

Serum uric acid can be elevated due to high fructose intake [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] , reduced excretion by the kidneys, and or high intake of dietary purine.

Added fructose can be found in processed foods and soda beverages as sucrose, or in some countries, as 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. [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]

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 fireflies.

The uric acid in urine can also dry in a baby's diaper to form a pinkish powder that is harmless.

ee also

* Hyperuricemia

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]