Recombinant Human TPMT protein

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Thiopurine S-methyltransferase often called TPMT plays a role as an enzyme that catalyzes the S-methylation of thiopurine compounds like 6-mercaptopurine and azathioprine. It exists as a monomer with a molecular mass of about 28 kDa. In humans TPMT expresses mainly in the liver and kidney. The activity of TPMT varies among individuals due to genetic polymorphisms.

Biological function summary

TPMT is important in the metabolism of therapeutic thiopurine drugs. These drugs often require precise dosing to achieve effectiveness without toxicity. TPMT does not form part of a larger complex; it functions independently to methylate thiopurine drugs. Genetic variations can lead to different TPMT activity levels affecting a person's response to these drugs significantly.

Pathways

TPMT is integral to the drug metabolism pathway specifically in the detoxification and elimination processes of thiopurine drugs. While TPMT predominantly acts on thiopurines thioredoxin reductase 1 (TXNRD1) may also have a role in modulating redox balance and affect the thiopurine metabolism indirectly through related cellular processes. Together they influence the cellular response to drugs like azathioprine.

Genetic variants in TPMT significantly contribute to thiopurine drug intolerance or toxicity particularly in conditions like inflammatory bowel disease and acute lymphoblastic leukemia where these drugs are used. Patients with low TPMT activity are at risk for severe myelosuppression a life-threatening bone marrow suppression. TPMT's relationship with the enzyme inosine monophosphate dehydrogenase (IMPDH) also illustrates its connection to nucleotide synthesis further linking TPMT to therapeutic outcomes in cancers.