Thiopurine methyltransferase

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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.

1 Pharmacology
2 Diagnostic use
3 References
4 External link

[edit] Pharmacology

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

[edit] Diagnostic use

Measurement of TPMT activity is encouraged prior to commencing azathioprine or 6-mercaptopurine, 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 about 5% of all thiopurine therapies will fail due to toxicity. This intolerant group could be anticipated by routine measurement of TPMT activity.

[edit] References

Mendelian Inheritance in Man (OMIM) 187680
Reuther LO, Vainer B, Sonne J, Larsen NE. Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity. Eur J Clin Pharmacol 2004;59:797-801. PMID 14634700.