TPMT Human

The TPMT enzyme is encoded by the TPMT gene located on chromosome 6 in humans . The gene provides instructions for making the TPMT enzyme, which carries out a specific chemical reaction known as S-methylation. This reaction involves the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to aromatic and heterocyclic sulphydryl compounds .

TPMT catalyzes the S-methylation of thiopurine drugs, converting them into inactive metabolites. The methyl donor in this reaction is SAM, which is converted to S-adenosyl-L-homocysteine as a byproduct . This process is essential for regulating the levels of active thiopurine drugs in the body and preventing toxicity.

The activity of TPMT varies among individuals due to genetic polymorphisms. Approximately 1 in 300 individuals is deficient in TPMT activity, which can lead to severe toxicity when treated with standard doses of thiopurine drugs . Therefore, TPMT testing is recommended before starting thiopurine therapy to determine the appropriate dosage and minimize adverse effects .

Recombinant human TPMT is produced using genetic engineering techniques, where the TPMT gene is inserted into a suitable expression system, such as bacteria or yeast. This allows for the production of large quantities of the enzyme for research and therapeutic purposes . Recombinant TPMT is used in various studies to understand the enzyme’s structure, function, and role in drug metabolism.

TPMT testing is particularly important in the treatment of inflammatory bowel disease (IBD), where thiopurines are often used to maintain remission . By guiding individual dosing according to pharmacogenetic data and monitoring drug metabolite levels, healthcare providers can optimize thiopurine therapy and improve patient outcomes .