Uricase

Uricase is an enzyme that catalyzes the oxidation of uric acid into allantoin. This reaction is significant in the metabolism of purines in some animals, facilitating the excretion of excess nitrogen. Uricase is present in most mammals and other organisms, but notably, it is absent in humans, great apes, and some breeds of dogs, which contributes to the higher levels of uric acid in these species. The absence of uricase in humans is associated with the condition gout, a type of arthritis caused by the accumulation of uric acid crystals in the joints.

Function

Uricase plays a crucial role in the purine degradation pathway, converting uric acid, which is relatively insoluble, into allantoin, a more soluble compound. This conversion allows organisms with uricase to efficiently eliminate excess nitrogen from the body, reducing the risk of conditions associated with high levels of uric acid.

Evolutionary Aspect

The loss of uricase activity in humans and some primates is believed to be due to a series of mutations in the uricase gene. This evolutionary change is thought to have advantages, such as the antioxidant properties of uric acid, which may have been beneficial for longevity. However, this comes at the cost of an increased risk of gout and possibly other metabolic conditions.

Clinical Significance

The absence of uricase in humans is a significant factor in the development of hyperuricemia and gout. Research into recombinant uricase has shown promise in treating these conditions by reducing uric acid levels in the blood. Pegloticase, a pegylated form of uricase, has been approved for clinical use in treating refractory chronic gout.

Recombinant Uricase

Recombinant uricase is produced through biotechnology and is used in the treatment of gout. Pegloticase, for example, is a modified form of uricase that has been pegylated to increase its solubility and decrease immunogenicity, allowing it to be used as a therapeutic agent in humans.

See Also

• Purine metabolism
• Gout
• Hyperuricemia
• Pegloticase

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