For treatment of hyperuricemia, reduces elevated plasma uric acid levels (from chemotherapy).
Examples of Clinical Use:
Drugs used to treat lympohoid leukemia, non-Hodgkin's lymphoma and acute myelogenous leukemia often lead to the accumulation of toxic plasma levels of purine metabolites (i.e. uric acid). The injection of the product reduces levels of uric acid and mitigates the toxic effects of chemotherapy induced tumor lysis.
Mechanism of action:
Rasburicase catalyzes enzymatic oxidation of uric acid into an inactive and soluble metabolite (allantoin).
Rasburicase is a crucial recombinant enzyme employed in the treatment of hyperuricemia, a condition associated with a high-level concentration of uric acid in the bloodstream.
Background of Rasburicase
Rasburicase was initially discovered as a fungal enzyme in Aspergillus species. Scientists noted its uricolytic activity, which led to its subsequent study and approval for medical use. Sanofi-Aventis first introduced it to the market under the name Elitek. The Food and Drug Administration (FDA) approved its medical application in the U.S in 2002.
Gene Locus and Protein Structure
The gene that encodes Rasburicase locates on Aspergillus species' genome. Specifically, the Rasburicase gene is located on the chromosome at locus 2q36.1. The protein structure of Rasburicase consists of an α/β barrel with eight α-helices and eight parallel β-strands. The structure also contains two histidine residues, His 141 and His 269, which are responsible for its uricolytic function.
Function of Rasburicase
Rasburicase works by catalyzing the oxidative reaction of uric acid into allantoin. Allantoin, a water-soluble substance, is then more readily excreted in the urine, thereby reducing high uric acid levels in the body. Importantly, this function of Rasburicase plays a pivotal role in managing hyperuricemia and tumor lysis syndrome (TLS), a potential life-threatening disorder frequently observed in cancer patients undergoing chemotherapy.
Rasburicase-Related Signaling Pathways
As an enzyme, Rasburicase does not directly involve any known signaling pathway. However, its impact on purine metabolism — by converting uric acid into allantoin — can indirectly influence multiple signaling pathways. The nucleotide metabolism pathway and xanthine dehydrogenase pathway are significantly affected by uric acid metabolisms, illustrating the indirect involvement of Rasburicase in these metabolic pathways.
Rasburicase has significant relevance to hyperuricemia and Tumor Lysis Syndrome (TLS). High uric acid levels often characterize both conditions. It plays an essential role in TLS, which is frequently seen in cancer treatments and blood-related disorders. By catalyzing uric acid's breakdown, Rasburicase helps to prevent complications associated with this condition.
List of Drug Candidates Related to Rasburicase
Several drugs interact with Rasburicase. They include Allopurinol, Xanthine oxidase inhibitors, and Lesinurad. Allopurinol is a xanthine oxidase inhibitor often prescribed alongside Rasburicase to help lower uric acid levels. Lesinurad, on the other hand, enhances uric acid kidney excretion and is used in tandem with xanthine oxidase inhibitors.
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