Why is uric acid produced

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This content does not have an English version. This content does not have an Arabic version. See more conditions. Request Appointment. Symptoms High uric acid level. Sections Basics Definition Causes When to see a doctor. Definition Causes When to see a doctor. Products and services. Replace sugary drinks with filtered water and fiber-rich smoothies.

Drinking plenty of fluids helps your kidneys flush out uric acid faster. Keep a water bottle with you at all times. Set an alarm every hour to remind you to take a few sips. Drinking alcohol can make you more dehydrated. It can also trigger high uric acid levels. This happens because your kidneys must first filter out products that occur in the blood due to alcohol instead of uric acid and other wastes.

Along with your diet, extra pounds can raise uric acid levels. Fat cells make more uric acid than muscle cells. Additionally, carrying extra pounds makes it harder for your kidneys to filter out uric acid.

Losing weight too quickly can also affect levels. Talk to a nutritionist about a healthy diet and weight loss plan that you can follow. Your doctor can recommend a healthy weight goal for your body type.

Have your blood sugar level checked when you visit your doctor. Adults with type 2 diabetes may have too much insulin in their bloodstream. This hormone is necessary to move sugar from your blood into your cells where it can power every bodily function.

However, too much insulin leads to excess uric acid in the body , as well as weight gain. Individuals with a condition called prediabetes may also have high insulin levels and a higher risk for type 2 diabetes.

Your doctor may want to check your serum insulin level in addition to your blood glucose level if insulin resistance is suspected. Eating more fiber will help your body get rid of uric acid. Fiber can also help balance your blood sugar and insulin levels. It also tends to increase satiety, helping to lower the risk of overeating. Add at least 5 to 10 grams of soluble fiber a day with whole foods such as:. Stress, poor sleeping habits, and too little exercise can increase inflammation.

This test checks to see how much uric acid you have in your blood. Another test can be used to check the level of uric acid in your urine. A blood sample is needed. Most of the time, blood is drawn from a vein located on the inside of the elbow or the back of the hand. This test is done to see if you have a high level of uric acid in your blood. High levels of uric acid can sometimes cause gout or kidney disease.

You may have this test if you have had or are about to have certain types of chemotherapy. Rapid destruction of cancerous cells or weight loss, which may occur with such treatments, can increase the amount of uric acid in your blood.

Normal value ranges may vary slightly among different laboratories. Talk to your provider about the meaning of your specific test results. The example above shows the common measurement range for results for these tests. An elevated serum uric acid is also one of the best independent predictors of diabetes and commonly precedes the development of both insulin resistance and diabetes type 2, as it was discovered that one quarter of diabetes cases can be attributed to a high serum uric acid level and elevated serum uric acid levels were found to be closely associated with insulin resistance and diabetes mellitus type 2 [] , [].

In response to controversial findings [] , a meta-analysis of prospective cohort studies [] and a recent critical review [] concluded that serum uric acid is a strong and independent risk factor for diabetes in middle-aged and older people.

Additionally, an increased serum uric acid level was significantly correlated with the severity of albuminuria and diabetic retinopathy in patients with type 2 diabetes mellitus []. In the liver, the enzyme ketohexokinase phosphorylates fructose, resulting in fall in levels of intracellular phosphates and ATP adenosine triphosphate. Decrease in intracellular phosphates activates adenosine monophosphate AMP deaminase, which catabolizes AMP to inosine monophosphate, and eventually to uric acid via the hypoxanthine-xanthine pathway [] , [].

Elevated amounts of intracellular uric acid are then released in the circulation, inducing inflammation in endothelial cells, kidney and vascular muscle fibers, and pancreas islets of Langerhans [].

Numerous clinical and experimental reports have documented association between high serum uric acid levels and non-alcoholic fatty liver disease NAFLD [30] , [31] , [32] , [33] , [34] , [35]. The ROS-TXNIP pathway inflammatory signaling induces deregulation of lipid metabolism-related gene expression and lipid accumulation [31] , [32] , [33] , through overexpression of the lipogenic enzyme, acetyl-coenzyme A COA carboxylase 1, fatty acid synthase and stearoyl-COA desaturase 1.

Another mechanism for uric acid-mediated fat accumulation in liver proposed that uric acid induces oxidative stress in hepatocytes endoplasmic reticulum followed by cleavage into active form and nuclear translocation of the transcription factor, sterol regulatory element-binding protein SREBP , which regulates the expression and activity of lipogenic enzymes [34]. Plasma fatty acid composition of people with NAFLD was recently shown to be associated with increase in omega-6 polyunsaturated fatty acids, especially arachidonic acid, compared to healthy controls [36] , [37].

The contribution of uric acid to development and progress of gout and metabolic syndrome appears to be well-established. The pivotal role of uric acid in preservation of the human species and the individual may be anticipated by the loss of the enzyme uricase in humans and the eagerness of the kidney to retrieve filtered uric acid.

Yet, studies are needed to document the paramount importance of uric acid in resistance to infectious, neurological and autoimmune diseases.

This article does not contain any studies with human or animal subjects. Rashika El Ridi , Ph. E-mail: rashika sci. Theses, and published 92 papers in international, peer-reviewed journals. Hatem Tallima , Ph. He has 35 publications in international, peer-reviewed journals, h index 15 and more than citations.

Peer review under responsibility of Cairo University. National Center for Biotechnology Information , U. Journal List J Adv Res v. J Adv Res. Published online Mar Author information Article notes Copyright and License information Disclaimer. Rashika El Ridi: ge. This article has been cited by other articles in PMC. Graphical abstract Uric acid, C 5 H 4 N 4 O 3 , 7,9-dihydro-1H-purine-2,6,8 3H -trione, molecular mass Da, is a product of the metabolic breakdown of purine nucleotides adenine and guanine.

Open in a separate window. Abstract Uric acid is synthesized mainly in the liver, intestines and the vascular endothelium as the end product of an exogenous pool of purines, and endogenously from damaged, dying and dead cells, whereby nucleic acids, adenine and guanine, are degraded into uric acid. Introduction Uric acid Fig. Endothelial function In contrast to studies documenting the ability of uric acid to impair vascular endothelial cells integrity [12] , a recent report indicated for the first time that extremely low levels of serum uric acid, attributed to loss-of-function mutations of SLC22A12 encoding blood vessels and kidney proximal tubular cells transporter, URAT1, cause endothelial dysfunction in vivo [13].

Potent mediator of type 2 immune responses Elevated concentration of uric acid was detected in the peritoneal cavity of mice following injection of the most widely used clinical adjuvant alum aluminum hydroxide [16] , [17]. Resistance to parasites The protective immune response against many helminth parasites is dependent on type 2 immune responses [23].

Defense against neurological and autoimmune diseases In support, plasma low uric acid levels, leading to decrease in antioxidant molecules, were evident in patients with multiple sclerosis.

Uric acid dread: Pathogenic potential of uric acid Gout Despite its documented protective potential, mentioning uric acid generates apprehension as it is the confirmed aetiological agent of the severe, acute and chronic inflammatory arthritis, gout. The alarming steps Recently, MSU crystals were identified as an endogenous danger signal formed after release of uric acid from dying cells.

Renal disorders The kidneys play a major role in the regulation of serum uric acid levels as approximately one third and two-thirds of the uric acid produced in humans is eliminated by the gastrointestinal tract and kidneys, respectively. The metabolic syndrome Metabolic syndrome is the name for a group of risk factors that raises the threat for heart disease and other health problems, such as diabetes and stroke.

Cardiovascular diseases Hyperuricemia was shown to be implicated in development of hypertension and cardiovascular diseases, via induction of growth factors, hormones, cytokines and autacoids [98] , [99] , [].

Insulin resistance and diabetes type 2 An elevated serum uric acid is also one of the best independent predictors of diabetes and commonly precedes the development of both insulin resistance and diabetes type 2, as it was discovered that one quarter of diabetes cases can be attributed to a high serum uric acid level and elevated serum uric acid levels were found to be closely associated with insulin resistance and diabetes mellitus type 2 [] , [].

Non-alcoholic fatty acid disease Numerous clinical and experimental reports have documented association between high serum uric acid levels and non-alcoholic fatty liver disease NAFLD [30] , [31] , [32] , [33] , [34] , [35]. Conclusions and future perspectives The contribution of uric acid to development and progress of gout and metabolic syndrome appears to be well-established.

Conflict of interest The authors have declared no conflict of interest. Compliance with Ethics Requirements This article does not contain any studies with human or animal subjects. Footnotes Peer review under responsibility of Cairo University. References 1. Chaudhary K. Uric Acid - key ingredient in the recipe for cardiorenal metabolic syndrome. Cardiorenal Med. Maiuolo J. Regulation of uric acid metabolism and excretion. Int J Cardiol. Chang B. Ancient insights into uric acid metabolism in primates.

Kratzer J. Evolutionary history and metabolic insights of ancient mammalian uricases. Ames B. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

Becker B. Towards the physiological function of uric acid. Free Radic Biol Med. Glantzounis G. Uric acid and oxidative stress. Curr Pharm Des. Sautin Y. Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucl Acids. Shi Y. Molecular identification of a danger signal that alerts the immune system to dying cells. Peden D. Uric acid is a major antioxidant in human nasal airway secretions.

Nasal secretion of the ozone scavenger uric acid. Am Rev Respir Dis. Oberbach A. A global proteome approach in uric acid stimulated human aortic endothelial cells revealed regulation of multiple major cellular pathways.

Sugihara S. Circ J. Iso T. Extremely low levels of serum uric acid are associated with endothelial dysfunction in humans. Nery R. Uric acid and tissue repair. Arq Bras Cir Dig. Kool M. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells.

J Exp Med. An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. Hara K. Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa. J Immunol. Gold M. Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization.

Mucosal Immunol. Willart M. Meth Mol Biol. Lambrecht B. Allergens and the airway epithelium response: gateway to allergic sensitization. J Allergy Clin Immunol. Hammad H. Barrier epithelial cells and the control of type 2 immunity.