TPMT does not transfer CH3 from AdoMet to 6MP

Stable Identifier
Reaction [transition]
Homo sapiens
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6-mercaptopurine (6MP) is used in the treatment of inflammatory diseases such as rheumatoid arthritis and childhood acute lymphoblastic leukemia. 6MP and its thioguanine nucleotide metabolites are principally inactivated by thiopurine methyltransferase (TPMT)-catalysed S-methylation. Defects in TPMT can cause thiopurine S-methyltransferase deficiency (TPMT deficiency; MIM:610460). Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs. Inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus. Variants that cause complete or almost complete loss of function are A154T and Y240C (variants TPMT*3B and 3C, together called TPMT*3A), A80P (TPMT*2) and A167G (TPMT*23) (Szumlanski et al. 1996, Tai et al. 1997, Lindquist et al. 2007).
Literature References
PubMed ID Title Journal Year
17885628 Explaining TPMT genotype/phenotype discrepancy by haplotyping of TPMT*3A and identification of a novel sequence variant, TPMT*23

Skoglund, K, Peterson, C, Karlgren, A, Kidhall, I, Söderkvist, P, Lindqvist, M, Almer, S

Pharmacogenet. Genomics 2007
9177237 Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity

Evans, WE, Tai, HL, Schuetz, EG, Yanishevski, Y, Krynetski, EY

Proc. Natl. Acad. Sci. U.S.A. 1997
8561894 Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism

Wieben, E, Brandriff, B, Szumlanski, C, Otterness, D, Her, C, Lennard, L, Kelsell, D, Lee, D, Weinshilboum, R, Spurr, N

DNA Cell Biol. 1996
Catalyst Activity

thiopurine S-methyltransferase activity of TPMT mutants [cytosol]

Normal reaction
Functional status

Loss of function of TPMT mutants [cytosol]

Name Identifier Synonyms
inherited metabolic disorder DOID:655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
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