Uricase (Urate Oxidase)

Uricase or urate oxidase is a hepatic enzyme meaning it is located in the liver and converts uric acid into allantoin. Allantoin is more efficiently excreted by the kidney because of how water soluble it is. However, in humans, a frameshift mutation during evolution affected the activity of the gene that encodes for uricase.

Function

It is an enzyme that converts uric acid to allantoin. Allantoin is much more soluble than uric acid, and passes harmlessly from the body. Unfortunately, during evolution, humans have lost the ability to produce uricase. The detailed mechanism consists of a copper binding enzyme catalyzing the oxidation or uric acid to 5-hydroxyisourate and hydrogen peroxide followed by the hydrolysis and decarboxylation leading to the formation of the desired product, allantoin.

Disease

If there is some damage to uricase or if it is absent in the body, it may be detrimental. Without a functioning uricase, there will be an excess amount of insoluble uric acid in the body which leads to a disease called gout. Gout is a form of inflammatory arthritis that develops in people who have high levels of uric acid in the blood. The acid forms needle-like crystals in joints and causes sudden, severe episodes of pain, redness, and swelling.

Uric acid is a waste material made by the breakdown of purines. Purines are found in foods high in protein. Gout occurs when uric acid accumulates which happens when there is more intake of uric acid than excreted uric acid. This leads to acute gout. The immune system recognizes it as a foreign product and attacks it. This will then lead to inflammation. The joint could be damaged or bone erosion could occur when the join is attacked.

Cure

There are many natural treatment options which include a decrease of purine intake, exercise, decrease smoking and alcohol intake, use of cherry juice (eliminate excess uric acid in blood). Another type of treatment available is gout therapy and medication. Pegloticase is a porcine uricase which is approved by the FDA for treatment of patients with gout. It must be administered by intravenous infusion every two weeks. Corticosteroids can also be taken by mouth or injected into an inflamed joint to relieve the pain and swelling of an acute gout attack. Corticosteroids and adrenocorticotropic hormones usually start working within 24 hours after corticosteroids have been taken.

Relevance

Uricase is an enzyme that catalyzes the conversion or uric acid to allantoin. Uric acid is an acidic waste product that your body passes through urine. It is a normal byproduct of the breakdown of foods that contain purines. Normally, the kidneys filter out uric acid from your blood; if too much builds up, it can lower the pH of your blood and urine and lead to a painful joint condition called gout and other complications. Interestingly, humans have naturally selected to terminate uricase. Because of the absence of uricase in humans, we may go through many complications caused by uric acid build up. Scientists are studying why natural selection would allow the accumulation of uric acid even though there are psychological complications of crystalized monosodium urate acutely causing liver and kidney damage or chronically causing gout.

Structural highlights

Uricase is mainly located in the liver where it forms an elctron dense crystalline core in peroxisomes. It is a tetramer of identical subunits each containing copper binding sites. One of the four identical subunits of the enzyme can be viewed . X-ray crystallography shows that uric acid binds to the active site as a monoanion and is deprotonated as a dianion which is then stabilized by This specific enzyme is found in Aspergillus flavus which is a type of bacteria. Uricase can be inhibited by both cyanide and chloride ions. Oxonate competitively inhibits uricase. This is without a ligand. You can view uricase with a ligand