Article: Thiopurine methyltransferase

Thiopurine methyltransferase, drawn from PDB 2BZG.

Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme (EC 2.1.1.67) that methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to S-adenosyl-L-homocysteine.

Pharmacology

TPMT is best known for its role in the metabolism of the drugs 6-mercaptopurine, azathioprine and 6-thioguanine.

Diagnostic use

Measurement of TPMT activity is encouraged prior to commencing this medication, as patients with low activity (10% prevalence) or especially absent activity (prevalence 0.3%) are at a heightened risk of drug-induced bone marrow toxicity due to accumulation of the unmetabolised drug. Reuther et al found that 5% of all cases of thiopurine toxicity could be anticipated by routine measurement of TPMT activity.