How is uric acid produced and excreted?
1. Introduction Uric acid production and metabolism are complex processes involving various factors that regulate hepatic production, as well as renal and gut excretion of this compound. Uric acid is the end product of an exogenous pool of purines and endogenous purine metabolism.
What is the role of uric acid in catabolism?
In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine. Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinar …
Is uric acid an end product of purine metabolism?
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.
Is uric acid increase associated with Metabolic Syndrome Pathophysiology?
Introduction: Uric acid (UA) increase is considered an important risk factor for the development of cardiovascular disease (CVD) favoring oxidative stress and endothelial dysfunction and is also involved in metabolic syndrome (MS) pathophysiology.
How is uric acid metabolized?
In humans the final compound of purines catabolism is uric acid. All other mammals possess the enzyme uricase that converts uric acid to allantoin that is easily eliminated through urine. Overproduction of uric acid, generated from the metabolism of purines, has been proven to play emerging roles in human disease.
Where does uric acid metabolism occur?
Normally, most daily uric acid disposal occurs via the kidneys. Humans cannot oxidize uric acid to the more soluble compound allantoin due to the lack of uricase enzyme.
Is uric acid produced in the liver?
Uric acid is generated from metabolic conversion of either exogenous (dietary) or endogenous purines, primarily in the liver and intestine. The immediate precursor of uric acid is xanthine, which is metabolized to uric acid by either xanthine oxidase or by its isoform, xanthine dehydrogenase.
Where is uric acid excreted?
Approximately two-thirds of uric acid is excreted by the kidneys, while the remaining one-third is excreted by intestinal uricolysis [2].
What enzyme breaks down uric acid?
uricaseIn many other mammals, however, there is an extra step in purine metabolism – the enzyme urate oxidase (or uricase) breaks down the uric acid into a soluble substance, allantoin.
Is uric acid excreted in humans?
In normal humans, uric acid is excreted in urine. However, uric acid excretion may be impaired by kidney disease, leading to hyperuricemia [2].
What causes overproduction of uric acid?
Most of the time, a high uric acid level occurs when your kidneys don't eliminate uric acid efficiently. Things that may cause this slow-down in the removal of uric acid include rich foods, being overweight, having diabetes, taking certain diuretics (sometimes called water pills) and drinking too much alcohol.
Does fatty liver cause high uric acid?
There is significantly positive correlation between serum uric acid levels and fatty liver index by Pearson's correlation coefficient (R = 0.513, p < 0.001). Correlation between fatty liver index, serum uric acid levels, waist circumference, and triglyceride.
What is the end product of uric acid?
Uric acid (UA) is the end product of the metabolic pathway for purines, the main constituents of nucleotides. The pathway of UA generation is shown in Figure 1. Briefly, inosine monophosphate (IMP) is derived from de novo purine synthesis and from purine salvage.
Why can't kidneys get rid of uric acid?
Kidney disease can lead to a high level of uric acid in your blood, so it is commonly associated with gout. When living with kidney disease, your kidneys aren't able to properly filter waste products, including uric acid, from your blood. This allows uric acid to build up, which may cause an attack of gout.
Is uric acid eliminated by kidneys?
Most circulating uric acid is freely filtered in the kidney, with roughly 90% of the filtered load normally reabsorbed along the nephron by mechanisms reviewed later in this article. Renal excretion of uric acid represents approximately 60–70% of total uric acid excretion from the body (6, 7).
How do kidneys process uric acid?
Overview. Uric acid moves through your blood to your kidneys. Your kidneys then add that uric acid to your urine, so it can leave the body. However, sometimes uric acid in the blood gets too high.
How is uric acid metabolism affected in gout?
Abstract. High plasma uric acid (UA) is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both.
What produces uric acid in the human body?
Uric acid is a normal body waste product. It forms when chemicals called purines break down. Purines are a natural substance found in the body. They are also found in many foods such as liver, shellfish, and alcohol.
Why uric acid is excreted in urine?
Uric acid, a weak organic acid, has very low pH-dependent solubility in aqueous solu- tions. About 70% of urate elimination occurs in urine, the kidney standing as a major deter- minant of plasma levels. The complex renal handling results in a fractional clearance of less than 10%.
How purines are degraded to uric acid in humans?
Uric acid, a product of purine metabolism, is degraded in most mammals by the hepatic enzyme urate oxidase (uricase) to more highly soluble allantoin, which is freely excreted in the urine.
What is the final compound of purines catabolism?
In humans the final compound of purines catabolism is uric acid. All other mammals possess the enzyme uricase that converts uric acid to allantoin that is easily eliminated through urine. Overproduction of uric acid , generated from the metabolism of purines, has been proven to play emerging roles in human disease.
What are the functions of purines?
Purines perform many important functions in the cell, being the formation of the monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines which also contribute to modulate energy metabolism and signal transduction, are structural components of some coenzymes and have been shown to play important roles in the physiology ...
Why do cells need purines?
All cells require a balanced quantity of purines for growth, proliferation and survival. Under physiological conditions the enzymes involved in the purine metabolism maintain in the cell a balanced ratio between their synthesis and degradation.
Does uric acid increase with cardiovascular disease?
In fact the increase of serum uric acid is inversely associated with disease sever ity and especially with cardiovascular disease states. This review describes the enzymatic pathways involved in the degradation of purines, getting into their structure and biochemistry until the uric acid formation.
How does uric acid increase?
Diet may be a factor. High intake of dietary purine, high-fructose corn syrup, and table sugar can increase levels of uric acid. Serum uric acid can be elevated by reduced excretion via the kidneys. Fasting or rapid weight loss can temporarily elevate uric acid levels.
What is the normal uric acid concentration?
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.
What percentage of people have gout?
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 gout, a painful condition resulting from needle-like crystals of uric acid precipitating in joints, capillaries, skin, and other tissues.
What is the normal uric acid level in blood?
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). 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.
What is the final product of purine metabolism?
In humans and higher primates, 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.
What enzyme catalyzes the formation of uric acid from xanthine and hypoxant?
Biochemistry. Xanthine oxidase is an enzyme which catalyzes the formation of uric acid from xanthine and hypoxanthine, which in turn are produced from other purines. Xanthine oxidase is a large enzyme whose active site consists of the metal molybdenum bound to sulfur and oxygen.
How much uric acid is excreted in dogs?
Normal excretion of uric acid in the urine is 250 to 750 mg per day (concentration of 250 to 750 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). Dogs.
Where can uric acid be found?
Uric acid can be ingested directly in the diet (especially in organ meats such as liver, kidney, and sweetbreads), or it can be produced in the body by two pathways involved in purine metabolism (Figure 1).
What is uric acid?
Uric acid is a by-product of purine metabolism in humans and certain apes who lack uricase, the enzyme that breaks down uric acid (Figure 1 ). When uric acid production is normal, and its clearance by the kidneys is normal, this metabolic quirk has no ill effects.
What is the product of purine metabolism?
Uric acid is a product of purine metabolism. In humans and higher-order primates, there is a tendency to retain high levels of serum uric acid due to the loss of akey enzyme, uricase, which converts uric acid to water soluble allantoin.
How is uric acid regulated?
Serum levels of uric acid are regulated by the balance between its production and excretion and is regulated by genetic and dietary factors. This chapter describes the biomedical importance of uric acid and health implications of hyperuricemia and gout. View chapter Purchase book. Read full chapter.
How does uric acid affect insulin?
Uric acid may contribute to insulin resistance in the liver by inducing mitochondrial oxidative stress and steatosis (adipose degeneration). Uric acid also blocks the ability of insulin to stimulate vasodilatation, which is important for the delivery of glucose to the skeletal muscle. Uric acid also induces inflammation in the adipose tissue with a reduction in the production of adiponectin (hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid oxidation). Finally, uric acid may also have direct effects on the pancreatic islet cells leading to local oxidative stress and islet dysfunction.
What is the end product of protein metabolism in birds?
In birds and reptiles, uric acid is the major end-product of protein metabolism. It is produced by the liver and excreted by kidney tubules; impaired elimination is an indication of renal disease. However, normal levels can be seen in early disease states. Approximately 90% of uric acid is secreted by the proximal tubules in avian species.
Which medication blocks the conversion of xanthine to uric acid by xanthine oxid?
The medication allopurinol, which blocks the conversion of xanthine to uric acid by xanthine oxidase, is effective because xanthine is far more soluble in aqueous solutions than is uric acid. Sign in to download full-size image. Figure 1. Simplified pathway of uric acid metabolism. PRPP, 5-phosphoribosyl- l -pyrophosphate.
Where does uric acid come from?
The endogenous production of uric acid is mainly from the liver, intestines and other tissues like muscles, kidneys and the vascular endothelium [1]. Uric acid is a C 5 H 4 N 4 O 3 (7,9-dihydro-1H-purine-2,6,8 (3H)-trione) heterocyclic organic compound with a molecular weight of 168 Da.
What is the solubility of uric acid in water?
The solubility of uric acid in water is low, and in humans, the average concentration of uric acid in blood is close to the solubility limit (6.8 mg/dL). When the level of uric acid is higher than 6.8 mg/dL, crystals of uric acid form as monosodium urate (MSU).
What is the end product of a pool of purines and endogenous purine metabolism?
Uric acid production and metabolism are complex processes involving various factors that regulate hepatic production, as well as renal and gut excretion of this compound. Uric acid is the end product of an exogenous pool of purines and endogenous purine metabolism.
How to measure uric acid concentration?
Uric acid concentration might be measured in serum, plasma, urine and in exhaled breath condensate. Determination of uric acid concentration includes phosphotungistic acid methods (PTA), uricase methods, high-performance liquid chromatography methods, dry chemistry systems and biosensor methods. Prior to determination of urate in urine, alkalinization of urine might be necessary, because of urate crystallize at pH lower than 5.75 [3]. The production and catabolism of purines are relatively constant between 300 and 400 mg per day. The kidneys eliminate approximately two-thirds, while the gastrointestinal tract eliminates one-third of the uric acid load. Almost all uric acid is filtered from glomeruli, while post-glomerular reabsorption and secretion regulate the amount of uric acid excretion. The proximal tubule is the site of uric acid reabsorption and secretion, and approximately 90% is reabsorbed into blood. This is primarily accomplished at the proximal tubular level by transporters that exchange intracellular anions for uric acid. Almost all reabsorption of uric acid occurs at the S1 segment of the proximal tubule. In the S2 segment of the proximal tubule, uric acid is secreted to a greater extent than that which undergoes reabsorption. Post-secretory reabsorption occurs at a more distal site of the proximal tubule, and approximately 10% of the filtered uric acid appears in the urine [1]. Hyperuricemia is a key risk factor for the development of gout, renal dysfunction, hypertension, hyperlipidemia, diabetes and obesity. Hyperuricemia occurs as a result of the increased uric acid production, the impaired renal uric acid excretion, or a combination of the two [4]. It is characterized by high uric acid level in the blood, causing deposition of urate crystals in the joints and kidneys [5]. Generally, hyperuricemia in adults is defined as a blood uric acid concentration greater than 7.0 mg/dL in men and 6.0 mg/dL in women. In normal humans, uric acid is excreted in urine. However, uric acid excretion may be impaired by kidney disease, leading to hyperuricemia [2].
What is the normal reference interval for uric acid?
The normal reference interval of uric acid in human blood is 1.5 to 6.0 mg/dL in women and 2.5 to 7.0 mg/dL in men.
Which organs eliminate the most uric acid?
The kidneys eliminate approximately two-thirds, while the gastrointestinal tract eliminates one-third of the uric acid load. Almost all uric acid is filtered from glomeruli, while post-glomerular reabsorption and secretion regulate the amount of uric acid excretion.
What are the functions of purines?
Purines perform many important functions in the cell, being the formation of the monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines which also contribute to modulate energy metabolism and signal transduction, are structural components of some coenzymes and have been shown to play important roles in the physiology ...
Where is uric acid produced?
Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinary tract. Several factors, including a high-fructose diet and the use of xenobiotics and alcohol, contribute to hyperuricaemia.
What is the role of uric acid in metabolism?
Uric acid as a modulator of glucose and lipid metabolism . In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine.
What is the final product of purine catabolism?
In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine.
What is the enzyme responsible for uric acid degradation?
Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects. In this review, we summarise the current knowledge of the effects of uric acid on the regulation of metabolism, primarily focusing on liver, adipose tissue and skeletal muscle.
Does uric acid affect lipid metabolism?
These studies have shown that high uric acid levels regulate the oxidative stress, inflammation and enzymes associated with glucose and lipid metabolism, suggesting a mechanism for the impairment of metabolic homeostasis . Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects.
Does uric acid cause metabolic syndrome?
Hyperuricaemia reduction in the Pound mouse or fructose-fed rats, as well as hyperuricaemia induction by uricase inhibition in rodents and studies using cell culture have suggested that uric acid plays an important role in the development of metabolic syndrome.
How does uric acid build up in the body?
Purines are chemical substances that occur naturally in the body and in some foods. When the body breaks down purines, this creates uric acid as a waste product. The kidneys filter it from the blood and pass it out of the body in the urine.
What is the process of uric acid?
Purines are chemical substances that occur naturally in the body and in some foods. When the body breaks down purines, this creates uric acid as a waste product. The kidneys filter it from the blood and pass it out of the body in the urine.
What are the symptoms of gout?
Symptoms of gout, which is linked to high uric acid levels, include: painful or swollen joints. joints that feel warm to the touch. shiny, discolored skin around the joints. Symptoms of a kidney stone, which high uric acid levels can also cause, include: back pain. pain in the side.
Why is my uric acid level high?
The causes of high uric acid levels are not always clear. However, genetics and environmental factors, such as diet and health, both play a part.
Why do you need a gout test?
A person may need the test if they have gout symptoms or kidney stones or are undergoing cancer treatment. The test does not carry any risks.
What is uric acid?
Uric acid is a waste product in the body. Sometimes, uric acid can build up in the joints and tissues, causing a range of health problems. These include gout, a form of arthritis.
What is the purpose of a needle and syringe for gout?
Doctors may sometimes also perform a joint aspiration, in which they use a needle and syringe to remove a small amount of fluid from the swollen joint. The presence of uric acid crystals in the fluid indicates gout.
Overview
Clinical significance and research
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). 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 ma…
Chemistry
Uric acid was first isolated from kidney stones in 1776 by Swedish chemist Carl Wilhelm Scheele. In 1882, the Ukrainian chemist Ivan Horbaczewski first synthesized uric acid by melting urea with glycine.
Uric acid displays lactam–lactim tautomerism (also often described as keto–enol tautomerism ). Although the lactim form is expected to possess some degree of aromaticity, uric acid crystalliz…
Biochemistry
Xanthine oxidase (found in mammals primarily as xanthine dehydrogenase and rarely as an oxidase ) is an enzyme which catalyzes the formation of uric acid from xanthine and hypoxanthine, which in turn are produced from other purines. Xanthine oxidase is a large enzyme whose active site consists of the metal molybdenum bound to sulfur and oxygen. Within cells, xanthine oxidase can exist as xanthine dehydrogenase and xanthine oxireductase, which has also been purified fr…
Genetic and physiological diversity
Primates. In humans and other great apes, 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. 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. Both uric acid and …
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; ABCG2; SLC17A1; SLC22A11; SLC22A12; SLC16A9; GCKR; LRRC16A; and PDZK1. GLUT9, encoded by the SLC2A9 gene, is know…
See also
• 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
External links
• Uric acid blood test – MedlinePlus
Chemistry
- Uric acid concentration might be measured in serum, plasma, urine and in exhaled breath condensate. Determination of uric acid concentration includes phosphotungistic acid methods (PTA), uricase methods, high-performance liquid chromatography methods, dry chemistry systems and biosensor methods. Prior to determination of urate in urine, alkalinizat...
Function
- Three urate transporters, URAT1/SLC22A12, GLUT9/SLC2A9, and ABCG2/BCRP, have been reported to play important roles in the regulation of serum uric acid (SUA), and their dysfunctions cause urate transport disorders. Among them, common dysfunction of ABCG2 exporter has proved to be a major cause of hyperuricemia and gout. Furthermore, renal hypouricemia is caus…
Cause
- In addition to problems with uric acid excretion due to kidney dysfunction, hyperuricemia can also result from the increased generation of uric acid. Diets heavy in purine or fructose, or exposure to lead can also contribute to high uric acid levels. Fructose is a unique sugar molecule in that it rapidly depletes ATP and increases the amounts of uric acid. In certain humans, a deficiency of …
Structure
- The second cytosolic isoform (cN-II) was the first nucleotidase to be described and purified. Through its activities hydrolyzes preferably 5-IMP, 5-GMP, 5-deoxy-IMP and 5-deoxy-GMP by adjusting the cell concentration of IMP and GMP [20]. cN-II gene is located on chromosome 10 [21]. Its mRNA is expressed in an ubiquitously manner with a higher expression in the pancreas, …
Genetics
- The gene for the fourth cytosolic isoform (cN-IV) is localized on chromosome 17 and its active enzyme is a dimeric deoxyribonucleotidase. The DNA sequence is formed by 5 exons and 4 introns [27].
Clinical significance
- Elevated serum levels of uric acid has been shown to play an important role in many disease states including gout and articular degenerative disorders as well as vascular inflammation and atherosclerosis. The balance of uric acid formation and excretion is driven by several enzymatic pathways which occur via different genetically-defined isoforms being also highly regulated by p…