TPMT does not transfer CH3 from AdoMet to 6MP

Stable Identifier
R-HSA-5603379
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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TPMT does not transfer CH3 from AdoMet to 6MP
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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

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

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

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

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

DNA Cell Biol. 1996
Participants
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Catalyst Activity

thiopurine S-methyltransferase activity of TPMT mutants [cytosol]

Physical Entity
TPMT mutants [cytosol] (Homo sapiens)
Activity
thiopurine S-methyltransferase activity (GO:0008119)
Normal reaction
TPMT transfers CH3 from AdoMet to 6MP (Homo sapiens)
Functional status

Loss of function of TPMT mutants [cytosol]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
inherited metabolic disorder DOID:655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
Cross References
Mondo
Authored
Jassal, B  (2014-07-01)
Reviewed
Nakaki, T  (2014-11-03)
Created
Jassal, B  (2014-07-01)
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