How is uric acid metabolized?

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.

What causes defective metabolism of uric acid?

Inborn Errors of Metabolism The condition is caused by a deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT),30 which leads to an overproduction of uric acid and the clinical features associated with this disorder (Table 24.1). Patients appear normal at birth and may develop normally for 6–8 months.

What disease is identified with uric acid metabolism?

Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease.

Which drug is used for increase metabolism of uric acid?

Allopurinol has been universally successful in lowering the serum uric acid concentration and uric acid excretion to normal levels, while not significantly affecting the clearance of urate or other aspects of renal function. Oxypurine excretion increased concomitantly with the fall in urine uric acid.

Where is purine metabolized?

liver
In mammals, excess purine nucleosides are removed from the body by breakdown in the liver and excretion from the kidneys. For most mammals, the purines are first converted into the intermediate uric acid, which is then metabolized by the enzyme uricase into the compound allantoin.

What is meant by purine metabolism?

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

What causes excess uric acid production?

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.

How is allopurinol metabolized?

Allopurinol undergoes metabolism in the liver, where it transforms into its pharmacologically active metabolite, oxypurinol. The half-life of allopurinol is 1 to 2 hours, and oxypurinol is about 15 hours. Both allopurinol and oxypurinol are renally excreted.

What is the purpose of purine metabolism?

Purine metabolism maintains cellular pools of adenylate and guanylate via synthesis and degradation of purine nucleotides. In mammalian cells, purine nucleotides are synthesized in two different pathways: the complementary salvage pathway and de novo biosynthetic pathway (Figure 1).

What happens when uric acid is high?

If too much uric acid stays in the body, a condition called hyperuricemia will occur. Hyperuricemia can cause crystals of uric acid (or urate) to form. These crystals can settle in the joints and cause gout, a form of arthritis that can be very painful. They can also settle in the kidneys and form kidney stones.

Which defects may lead to hyperuricemia?

Enzymatic defects such as glycogenoses type I and aldolase-B deficiency are other causes of hyperuricemia that result from a combination of overproduction and underexcretion. Urate crystals can engage an intracellular pattern recognition receptor, the macromolecular NALP3 (cryopyrin) inflammasome complex.

Which diuretic does not increase uric acid?

Evidence-Based Answer. Thiazide diuretics may be used in most patients with hypertension who have only minimally increased risk of gout.

Is allopurinol metabolized by the kidneys?

As allopurinol and its metabolites are primarily eliminated by the kidney, accumulation of the drug can occur in renal failure. Hence, the US Food and Drug Administration (FDA) recommends that the dose of allopurinol should be reduced in people with CKD.

Which enzyme is inhibited by allopurinol?

Allopurinol, a purine analog, is a structural isomer of hypoxanthine and inhibits xanthine oxidase enzyme.