A nucleoside analogue that is being screened as a potential anticancer agent causes gout in clinical trials. Which of the following actions of this drug may cause gout?

Question

Quizplus · Accepted Answer

Interference with feedback control of PRPP synthesis can lead to increased purine synthesis, resulting in excess uric acid production, which can cause gout. Both the salvage and de novo synthesis pathways of purine metabolism utilize an activated sugar intermediate, 5-phosphoribosyl-1-pyrophosphate (PRPP). PRPP is generated by the action of PRPP synthetase. The synthesis of PRPP by PRPP synthetase is feedback inhibited by purine-5′-nucleotides (predominantly AMP and GMP) and activated by ribose-5-phosphate. Inhibition of purine salvage pathways leads to a reduction in the production of purine-5′-nucleotides, resulting in reduced inhibition of PRPP synthetase. Higher activity of PRPP synthetase results in excess purine nucleotide synthesis and as a consequence, increased catabolism of the excess purines to uric acid, resulting in hyperuricemia (gout)

A Nucleoside Analogue That Is Being Screened as a Potential