Uric acid is a

heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with o ...

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

, and

hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...

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 Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...

s, and it is a normal component of

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

. High blood concentrations of uric acid can lead to

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...

and are associated with other medical conditions, including

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

and the formation of ammonium acid urate

kidney stones Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

Chemistry

Uric acid was first isolated from

kidney stone Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

s in 1776 by Swedish chemist

Carl Wilhelm Scheele Carl Wilhelm Scheele (, ; 9 December 1742 – 21 May 1786) was a Swedish German pharmaceutical chemist. Scheele discovered oxygen (although Joseph Priestley published his findings first), and identified molybdenum, tungsten, barium, hydrog ...

. In 1882, the Ukrainian chemist Ivan Horbaczewski first synthesized uric acid by melting

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important r ...

with

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

. Uric acid displays lactam–lactim

tautomerism Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hyd ...

(also often described as

keto–enol tautomerism In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...

). Although the lactim form is expected to possess some degree of

aromaticity In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

, uric acid crystallizes in the lactam form, with

computational chemistry Computational chemistry is a branch of chemistry that uses computer simulation to assist in solving chemical problems. It uses methods of theoretical chemistry, incorporated into computer programs, to calculate the structures and properties of m ...

also indicating that tautomer to be the most stable. Uric acid is a

diprotic acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...

with p''K''_a1 = 5.4 and p''K''_a2 = 10.3, thus at physiological pH, it predominately exists as the monoionic urate ion. :

Water solubility

In general, the water

solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubil ...

of uric acid and its

alkali metal The alkali metals consist of the chemical elements lithium (Li), sodium (Na), potassium (K),The symbols Na and K for sodium and potassium are derived from their Latin names, ''natrium'' and ''kalium''; these are still the origins of the names ...

and

alkaline earth The alkaline earth metals are six chemical elements in group 2 of the periodic table. They are beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).. The elements have very similar properties: they are al ...

salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...

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 Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

is very low or negligible. In ethanol/water mixtures, the solubilities are somewhere between the end values for pure ethanol and pure water. : 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.

Biochemistry

Xanthine oxidase Xanthine oxidase (XO, sometimes XAO) 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 xanthin ...

(found in mammals primarily as xanthine dehydrogenase and rarely as an oxidase) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

which catalyzes the formation of uric acid from

xanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine ...

and

hypoxanthine Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-hydroxypurine. ...

, which in turn are produced from other

s. Xanthine oxidase is a large enzyme whose

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

consists of the metal

molybdenum Molybdenum is a chemical element with the symbol Mo and atomic number 42 which is located in period 5 and group 6. The name is from Neo-Latin ''molybdaenum'', which is based on Ancient Greek ', meaning lead, since its ores were confused with lea ...

bound to

sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

and oxygen. Within cells, xanthine oxidase can exist as xanthine dehydrogenase and xanthine oxireductase, which has also been purified from

bovine Bovines (subfamily Bovinae) comprise a diverse group of 10 genera of medium to large-sized ungulates, including cattle, bison, African buffalo, water buffalos, and the four-horned and spiral-horned antelopes. The evolutionary relationship betwe ...

milk and

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

extracts. Uric acid is released in

hypoxic Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the t ...

conditions (low oxygen saturation).

Genetic and physiological diversity

Primates

humans Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

and other

great apes The Hominidae (), whose members are known as the great apes or hominids (), are a taxonomic family of primates that includes eight extant species in four genera: '' Pongo'' (the Bornean, Sumatran and Tapanuli orangutan); ''Gorilla'' (the ...

, uric acid (actually hydrogen urate ion) is the final

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

(breakdown) product of

purine metabolism Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms. Biosynthesis Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to r ...

and is excreted in urine, whereas in most other

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s, the enzyme

uricase The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate: :Uric acid + O2 + H2O → 5-hydroxyisourate + H2O2 :5-hydroxyisourate + H2O → allan ...

further oxidizes uric acid to

allantoin Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid. Allantoin is a major metabolic intermediate in most organisms including animals, plants and bacter ...

. The loss of uricase in higher primates parallels the similar loss of the ability to synthesize

ascorbic acid Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...

, leading to the suggestion that urate may partially substitute for ascorbate in such species. Both uric acid and ascorbic acid are strong

reducing agent In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ). Examples of substances that are commonly reducing agents include the Earth meta ...

s (

electron donor In chemistry, an electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process. Typical reducing agents undergo permanent chemi ...

s) and potent

antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...

s. In humans, over half the antioxidant capacity of

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...

comes from hydrogen urate ion.

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 (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 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&nbs ...

. 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

Dogs

The Dalmatian has a genetic defect in uric acid uptake by the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

and

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

s, resulting in decreased conversion to

, so this breed excretes uric acid, and not allantoin, in the urine.

Birds and reptiles

bird Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...

s and

reptile Reptiles, as most commonly defined are the animals in the class Reptilia ( ), a paraphyletic grouping comprising all sauropsids except birds. Living reptiles comprise turtles, crocodilians, squamates (lizards and snakes) and rhynchocephalians ( ...

s, and in some desert-dwelling mammals (such as the

kangaroo rat Kangaroo rats, small mostly nocturnal rodents of genus ''Dipodomys'', are native to arid areas of western North America. The common name derives from their bipedal form. They hop in a manner similar to the much larger kangaroo, but developed t ...

), 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 In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...

that is energetically costly in comparison to processing of other nitrogenous wastes such as

(from the

urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of Biochemistry, biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle ...

) or

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

, but has the advantages of reducing water loss and preventing dehydration.

Invertebrates

Platynereis dumerilii ''Platynereis dumerilii'' is a species of annelid polychaete worm. It was originally placed into the genus ''Nereis'' and later reassigned to the genus '' Platynereis''. ''Platynereis dumerilii'' lives in coastal marine waters from temperate t ...

'', a marine

polychaete Polychaeta () is a paraphyletic class of generally marine annelid worms, commonly called bristle worms or polychaetes (). Each body segment has a pair of fleshy protrusions called parapodia that bear many bristles, called chaetae, which are made ...

worm, uses uric acid as a sexual

pheromone A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

. The female of the species releases uric acid into the water during

mating In biology, mating is the pairing of either opposite-sex or hermaphroditic organisms for the purposes of sexual reproduction. ''Fertilization'' is the fusion of two gametes. ''Copulation'' is the union of the sex organs of two sexually reproduc ...

, to induce males to release sperm.

Genetics

Although foods such as meat and seafood can elevate serum urate levels, genetic variation is a much greater contributor to high serum urate. 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 Solute carrier family 2, facilitated glucose transporter member 9 is a protein that in humans is encoded by the ''SLC2A9'' gene. This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a signifi ...

''; '' ABCG2''; ''

SLC17A1 Sodium-dependent phosphate transport protein 1 is a protein that in humans is encoded by the ''SLC17A1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." m ...

''; ''

SLC22A11 Solute carrier family 22 member 11 is a protein that in humans is encoded by the ''SLC22A11'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gen ...

''; ''

SLC22A12 Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the ''SLC22A12'' gene. Function The protein encoded by this gene is a uric acid, urate transpor ...

''; ''

SLC16A9 Monocarboxylate transporter 9 (MCT9, solute carrier family 16, member 9, SLC16A9) is a protein that in humans is encoded by the ''SLC16A9'' gene. Clinical relevance Mutations in the SLC16A9 gene have been associated with carnitine Carniti ...

''; ''

GCKR The glucokinase regulatory protein (GKRP) also known as glucokinase (hexokinase 4) regulator (GCKR) is a protein produced in hepatocytes (liver cells). GKRP binds and moves glucokinase (GK), thereby controlling both activity and intracellular locat ...

''; ''

LRRC16A CARMIL1 is a protein that in humans is encoded by the ''CARMIL1'' gene. The gene is also known as LRRC16, LRRC16A, CARMIL, or CARMIL1a. Model organisms Model organisms have been used in the study of CARMIL1 function. A conditional knockout mouse ...

''; and ''

PDZK1 Na(+)/H(+) exchange regulatory cofactor NHE-RF3 is a protein that in humans is encoded by the ''PDZK1'' gene. Interactions PDZK1 has been shown to interact with: * AKAP10, * CLCN3, * Cystic fibrosis transmembrane conductance regulator * FARP ...

''. GLUT9, encoded by the ''SLC2A9'' gene, is known to transport both uric acid and

fructose Fructose, or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galacto ...

. Myogenic

, as a result of the

Purine Nucleotide Cycle Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines a ...

running when ATP reservoirs in muscle cells are low, is a common pathophysiologic feature of glycogenoses such as GSD-III, GSD-V and GSD-VII, as they are metabolic myopathies which impair the ability of ATP (energy) production for the muscle cells to use.Mineo I, Kono N, Hara N, Shimizu T, Yamada Y, Kawachi M, Kiyokawa H, Wang YL, Tarui S. Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII. N Engl J Med. 1987 Jul 9;317(2):75-80. doi: 10.1056/NEJM198707093170203. 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 IMP (inosine monophosphate) is converted into uric acid. IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid

Clinical significance and research

In human

, the

reference range In medicine and health-related fields, a reference range or reference interval is the range or the interval of values that is deemed normal for a physiological measurement in healthy persons (for example, the amount of creatinine in the blood, o ...

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). Uric acid concentrations in blood plasma above and below the normal range are known as, respectively,

and

hypouricemia 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 thres ...

. Likewise, uric acid concentrations in urine above and below normal are known as

hyperuricosuria 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 dissol ...

and hypouricosuria. Uric acid levels in saliva may be associated with blood uric acid levels.

High uric acid

Hyperuricemia 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&nbs ...

(high levels of uric acid), which induces

, has various potential origins: * Diet may be a factor. High intake of dietary

high-fructose corn syrup High-fructose corn syrup (HFCS), also known as glucose–fructose, isoglucose and glucose–fructose syrup, is a sweetener made from corn starch. As in the production of conventional corn syrup, the starch is broken down into glucose by enzy ...

, and

sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refined ...

can increase levels of uric acid. * Serum uric acid can be elevated by reduced excretion via the

s. * Fasting or rapid weight loss can temporarily elevate uric acid levels. * Certain drugs, such as

thiazide Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

diuretics, can increase blood uric acid levels by interfering with

renal clearance In pharmacology, clearance is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time. Usually, clearance is measured in L/h or mL/min. The quantity reflects the rate of drug elimination d ...

. *

Tumor lysis syndrome 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 blood ...

, a metabolic complication of certain cancers or chemotherapy, due to

nucleobase Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic b ...

and potassium release into the plasma. * Low ATP (energy) reservoirs activating the

to produce ATP from adenine nucleotides (AMP, IMP, and S-AMP).Johnson TA, Jinnah HA, Kamatani N. Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP. Front Pharmacol. 2019 Feb 19;10:98. doi: 10.3389/fphar.2019.00098. PMID: 30837873; PMCID: PMC6390775. Low ATP reservoirs can be due to strenuous exercise, fasting or starvation, or impairment of ATP production such as metabolic myopathies,

, scurvy (Vitamin C deficiency),Travica N, Ried K, Sali A, Scholey A, Hudson I, Pipingas A. Vitamin C Status and Cognitive Function: A Systematic Review. Nutrients. 2017 Aug 30;9(9):960. doi: 10.3390/nu9090960. PMID: 28867798; PMCID: PMC5622720.Pietrzak I, Opala G. Rola karnityny w przemianie lipidowej u człowieka he role of carnitine in human lipid metabolism Wiad Lek. 1998;51(1-2):71-5. Polish. PMID: 9608835. and excessive alcohol consumption.Zakhari S. Overview: how is alcohol metabolized by the body? Alcohol Res Health. 2006;29(4):245-54. PMID: 17718403; PMCID: PMC6527027. Excess IMP (inosine monophosphate) is converted into uric acid. IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid

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. Excess blood uric acid can induce

, a painful condition resulting from needle-like crystals of uric acid precipitating in

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw ...

capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

, and other tissues. 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. 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. Purine-rich foods include liver, kidney, and sweetbreads, and certain types of seafood, including anchovies, herring, sardines, mussels, scallops, trout, haddock, mackerel, and tuna. 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 Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid el ...

salts; lithium urate is more soluble. Today, inflammation during attacks is more commonly treated with

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

colchicine Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken b ...

, or

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...

s, and urate levels are managed with

allopurinol 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 by mouth ...

. Allopurinol, which weakly inhibits xanthine oxidase, is an analog of hypoxanthine that is hydroxylated by

xanthine oxidoreductase Xanthine oxidase (XO, sometimes XAO) 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 xanthin ...

at the 2-position to give oxipurinol.

Tumor lysis syndrome

, an emergency condition that may result from

blood cancer Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...

s, produces high uric acid levels in blood when tumor cells release their contents into the blood, either spontaneously or following

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

. Tumor lysis syndrome may lead to

acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are c ...

when uric acid crystals are deposited in the kidneys. Treatment includes hyperhydration to dilute and excrete uric acid via

rasburicase Rasburicase (trade names 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 kn ...

to reduce levels of poorly soluble uric acid in blood, or

to inhibit

catabolism from adding to uric acid levels.

Lesch–Nyhan syndrome

Lesch–Nyhan syndrome 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 ...

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

Cardiovascular disease

Hyperuricemia is associated with an increase in

risk factors In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...

for

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

. 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.

Type 2 diabetes

Hyperuricemia may be a consequence of insulin resistance in

rather than its precursor. One study showed high serum uric acid was associated with higher risk of

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...

, independent of

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

dyslipidemia Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary ar ...

, and

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

. Hyperuricemia is associated with components of

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndrome ...

, including in children.

Uric acid stone formation

Kidney stone Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

s can form through deposits of sodium urate microcrystals. Saturation levels of uric acid in blood may result in one form of

s when the urate crystallizes in the kidney. These uric acid stones are

radiolucent Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...

, so do not appear on an abdominal plain

X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

. Uric acid crystals can also promote the formation of

calcium oxalate Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula . It forms hydrates , where ''n'' varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydrate ...

stones, acting as "seed crystals".

Metabolic Myopathies

Metabolic myopathies, such as glycogenoses, impair the ability of the muscle cell to create ATP (energy). When ATP reservoirs are low, ATP is produced via the

. 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 IMP (inosine monophosphate) is converted into uric acid. IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid

Excessive Alcohol Consumption

Hyperuricemia can be caused by excessive alcohol consumption by converting

→ acetaldehyde → acetate decreasing the amount of NAD⁺ available. NAD⁺ is needed for the

Krebs Cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

to produce energy via

oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine tri ...

. With impairment of the Krebs Cycle, this leads the ATP reservoir to become low, activating the

. Excess IMP (inosine monophosphate) is converted into uric acid. IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid

Scurvy (Vitamin C Deficiency)

Vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...

acts as a reducing agent, donating electrons in various enzymatic and non-enzymatic reactions. It is a cofactor for at least eight enzymatic reactions involved in key bodily processes including the production of collagen, preventing harmful genetic mutations, protecting white blood cells and the production of

carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ...

, vital for energy. Carnitine plays a crucial role in lipid metabolism. As scurvy reduces the production of carnitine, the ability of the body to utilize fats for energy is impaired, leading to a low ATP reservoir. When ATP reservoirs are low, ATP is produced via the

. Excess IMP (inosine monophosphate) is converted into uric acid. IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid

Low uric acid

Low uric acid (

) can have numerous causes. Low dietary

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

intakes cause lower uric acid levels. This effect can be even more pronounced in women taking oral contraceptive medication.

Sevelamer Sevelamer (rINN) is a phosphate binding medication used to treat hyperphosphatemia in patients with chronic kidney disease. When taken with meals, it binds to dietary phosphate and prevents its absorption. Sevelamer was invented and developed by ...

, a drug indicated for prevention of

hyperphosphataemia Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. Often there is also low calcium levels which can ...

in people with

chronic kidney failure Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...

, can significantly reduce serum uric acid.

Multiple sclerosis

Meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of 10 case-control studies found that the serum uric acid levels of patients with

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

were significantly lower compared to those of healthy controls, possibly indicating a diagnostic

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...

for multiple sclerosis.

Normalizing low uric acid

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

References

External links

Uric acid blood test – MedlinePlus
{{DEFAULTSORT:Uric Acid Nitrogen cycle Organic acids Triketones

Chemistry

Water solubility

Biochemistry

Genetic and physiological diversity

Primates

Humans

Dogs

Birds and reptiles

Invertebrates

Genetics

Clinical significance and research

High uric acid

Gout

Tumor lysis syndrome

Lesch–Nyhan syndrome

Cardiovascular disease

Type 2 diabetes

Uric acid stone formation

Metabolic Myopathies

Excessive Alcohol Consumption

Scurvy (Vitamin C Deficiency)

Low uric acid

Multiple sclerosis

Normalizing low uric acid

See also

References

External links