Question

6-Mercaptopurine (Box 23-2), after its conversion to the corresponding nucleotide through salvage reactions, is a potent competitive inhibitor of IMP in the pathways for AMP and GMP biosynthesis. It is therefore a clinically useful anticancer agent. The chemotherapeutic effectiveness of 6-mercaptopurine is enhanced when it is administered with allopurinol. Explain the mechanism of this enhancement.

Short answer

Allopurinol also suppresses the synthesis of IMP by acting as a hypoxanthine analogue.

Step-by-step solution

Describe Allopurinol.

Allopurinol is a hypoxanthine analogue with the N7 and C8 locations switched around.

The metabolism.

In the salvage pathway, hypoxanthine can be transformed to inosine monophosphate (IMP) via hypoxanthine-guanine phosphoribosyltransferase. As a result, allopurinol inhibits hypoxanthine-guanine phosphoribosyltransferase, which inhibits the formation of IMP.

Because allopurinol also suppresses the synthesis of IMP by acting as a hypoxanthine analogue, the chemotherapeutic effectiveness of -mercaptopurine is increased when it is given with allopurinol.