Manjul Cyrusi

Gout is a metabolic disorder that causes a painful and common type of arthritis. It is caused when there is too much uric acid in the blood. This is called hyperuricemia. Uric acid is a breakdown product of normal metabolism in the body and is normally excreted through urine. Buildup of uric acid results in needlelike crystals forming in the joints, soft tissues, and organs.

Cases of gout have increased in recent years. This increase is likely due to an aging population, dietary and lifestyle changes, the rising incidence of obesity, greater use of medicines, such as diuretics (water pills), all of which can lead to a high uric acid level in the body.

Metabolism of Purines

The process leading to hyperuricemia and gout begins with the metabolism, or breakdown, of purines. Purines are compounds that are important for energy. They are part of the nucleic acids (DNA and RNA) that are present in all cells of the body. Purines can be divided into two types:

The process of breaking down purines results in the formation of uric acid in the body. Most mammals, except humans, have an enzyme called uricase. Uricase breaks down uric acid so it can be easily removed from the body. Because humans lack uricase, uric acid is not easily removed and can build up in body tissues.

Uric Acid and Hyperuricemia

Purines in the liver are converted to uric acid. The uric acid enters the bloodstream. Most of the uric acid goes through the kidneys and is excreted in urine. The remaining uric acid travels through the intestines where bacteria help break it down.

The enzyme responsible for production of uric acid from purines is xanthine oxidase. This enzyme is the target of urate-lowering treatments such as allopurinol.

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