Information on EC 2.1.1.67 - thiopurine S-methyltransferase

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The expected taxonomic range for this enzyme is: Mammalia

EC NUMBER
COMMENTARY
2.1.1.67
-
RECOMMENDED NAME
GeneOntology No.
thiopurine S-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
also acts, more slowly, on thiopyrimidines and aromatic thiols. Not identical with EC 2.1.1.9 thiol S-methyltransferase
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Drug metabolism - other enzymes
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:thiopurine S-methyltransferase
Also acts, more slowly, on thiopyrimidines and aromatic thiols. Not identical with EC 2.1.1.9 thiol S-methyltransferase.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6-thiopurine transmethylase
-
-
-
-
mercaptopurine methyltransferase
-
-
-
-
thiopurine methyltransferase
-
-
-
-
TPMT
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
67339-09-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
293T cells; HeLa cells; human
-
-
Manually annotated by BRENDA team
natural variant Glu28Val, TPMT*13; natural variant Gly144Arg, variant TPMT*10; natural variant His227Gln, variant TPMT*7; natural variant Ser125Leu, variant TPMT*12; wild-type variant
-
-
Manually annotated by BRENDA team
variant Arg163His, i.e. variant TPMT*16, loss-of function allele of TPMT, patients heterozygous for the Arg163His mutation are intermediate methylators; variant Lys122Thr, i.e. variant TPMT*19, missense mutation in patients with Crohn's disease, patients heterozygous for the Lys122Thr mutation have normal TPMT activity; wild-type variant TPMT*1
UniProt
Manually annotated by BRENDA team
mouse; mouse, strain C57/BL6, GenBank accession number
Uniprot
Manually annotated by BRENDA team
mouse; Swiss-Webster
-
-
Manually annotated by BRENDA team
NIH-3T3 cells
-
-
Manually annotated by BRENDA team
Mus musculus Swiss-Webster
Swiss-Webster
-
-
Manually annotated by BRENDA team
rat, Sprague-Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
when thiopurine methyltransferase protein activity is low a greater degree of cytotoxicity and DNA damage can occur after thioguanine exposure
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 2,8-dihydroxy-6-thiopurine
S-adenosyl-L-homocysteine + 2,8-dihydroxy-6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-amino-6-thiopurine
S-adenosyl-L-homocysteine + 2-amino-6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-aminothiophenol
S-adenosyl-L-homocysteine + 2-methylsulfanylphenylamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-bromothiophenol
S-adenosyl-L-homocysteine + 1-bromo-2-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-mercaptoethanol
S-adenosyl-L-homocysteine + 2-methylmercaptoethanol
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-methoxythiophenol
S-adenosyl-L-homocysteine + 1-methoxy-2-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-thiothymine
S-adenosyl-L-homocysteine + 2-methylthiothymine
show the reaction diagram
Mus musculus, Rattus norvegicus, Mus musculus Swiss-Webster
-
-
-
-
?
S-adenosyl-L-methionine + 2-thiouracil
S-adenosyl-L-homocysteine + thiouracil-2-S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-thiouracil
S-adenosyl-L-homocysteine + thiouracil-2-S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-thiouracil
S-adenosyl-L-homocysteine + thiouracil-2-S-methylether
show the reaction diagram
Rattus norvegicus, Mus musculus Swiss-Webster
-
-
-
-
?
S-adenosyl-L-methionine + 3-methoxythiophenol
S-adenosyl-L-homocysteine + 1-methylsulfanyl-3-methoxybenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-(aminomethoxy)thiophenol
S-adenosyl-L-homocysteine + 1-aminomethoxy-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-bromothiophenol
S-adenosyl-L-homocysteine + 1-bromo-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-chlorothiophenol
S-adenosyl-L-homocysteine + 1-chloro-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-fluorothiophenol
S-adenosyl-L-homocysteine + 1-fluoro-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-methoxythiophenol
S-adenosyl-L-homocysteine + 1-methoxy-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-methylthiophenol
S-adenosyl-L-homocysteine + 1-methyl-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-nitrothiophenol
S-adenosyl-L-homocysteine + 1-methylsulfanyl-4-nitrobenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-thiobenzoate
S-adenosyl-L-homocysteine + 4-methylsulfanyl benzoate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-hydroxy-8-mercaptopurine
S-adenosyl-L-homocysteine + 6-hydroxy-8-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
O55060
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
O55060
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
P51580
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
immunosuppressant medication
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
inactivation
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
azathioprine is converted via a non-enzymatic reaction to mercaptopurine, which is subsequently metabolized through TPMT
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
TPMT deactivates 6-mercaptopurine by methylation
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine nucleoside
S-adenosyl-L-homocysteine + 6-methylmercaptopurine nucleoside
show the reaction diagram
-
inactivation
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine-riboside
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine-riboside-5'-monophosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-riboside-5'-monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine-riboside-5'-triphosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-riboside-5'-triphosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-selenoguanine-riboside
S-adenosyl-L-homocysteine + 6-methylselenoguanine-riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-selenopurine
S-adenosyl-L-homocysteine + 6-methylselenopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-selenopurine-riboside
S-adenosyl-L-homocysteine + 6-methylselenopurine-riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiodeoxyguanosine monophosphate
S-adenosyl-L-homocysteine + 6-methylthiodeoxyguanosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiodeoxyinosine monophosphate
S-adenosyl-L-homocysteine + 6-methyl thiodeoxyinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
O55060
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
P51580
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
P51580
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
Mus musculus Swiss-Webster
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine monophosphate
S-adenosyl-L-homocysteine + 6-methylthioguanine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine-riboside
S-adenosyl-L-homocysteine + 6-methylthioguanine-riboside
show the reaction diagram
-
-
-
-
-
S-adenosyl-L-methionine + 6-thioguanine-riboside
S-adenosyl-L-homocysteine + 6-methylthioguanine-riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine-riboside-5'-monophosphate
S-adenosyl-L-homocysteine + 6-methylthioguanine-riboside-5'-monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanosine monophosphate
S-adenosyl-L-homocysteine + 6-methyl thioguanosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine riboside
show the reaction diagram
-
-
-
-
-
S-adenosyl-L-methionine + 6-thioinosine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine 5'-monophosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine ribonucleotide
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine monophosphate
S-adenosyl-L-homocysteine + 6-methyl thioinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine monophosphate
S-adenosyl-L-homocysteine + 6-methylthioinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine-monophosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-ribonucleotides
show the reaction diagram
-
-
consisting of 6-methyl-thioinosine-monophosphate, -diphosphate and triphosphate
-
?
S-adenosyl-L-methionine + 6-thioinosine-monophosphate
S-adenosyl-L-homocysteine + 6-methylthioinosine-monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiopurine
S-adenosyl-L-homocysteine + 6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiopurine
S-adenosyl-L-homocysteine + 6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiopurine
S-adenosyl-L-homocysteine + 6-methylthiopurine
show the reaction diagram
Mus musculus, Rattus norvegicus, Mus musculus Swiss-Webster
-
preferred substrate
-
-
?
S-adenosyl-L-methionine + 6-thiouric acid
S-adenosyl-L-homocysteine + 6-methylthiouric acid
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 7-methyl-6-mercaptopurine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 8-hydroxy-6-mercaptopurine
S-adenosyl-L-homocysteine + 8-hydroxy-6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 9(n-propyl)6-thioguanine
S-adenosyl-L-homocysteine + 9(n-propyl)6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 9-(n-butyl)-6-mercaptopurine
S-adenosyl-L-homocysteine + 9-(n-butyl)-6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 9-ethyl-6-mercaptopurine
S-adenosyl-L-homocysteine + 9-ethyl-6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
O55060
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
P51580
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
specific for S-adenosyl-L-methionine
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
enzyme plays an important role in metabolism of heterocyclic sulfhydryl drugs such as 6-thiopurine and 6-thioguanine
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
S-methylation, enzyme of major catabolic pathway of thiopurines
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
Mus musculus Swiss-Webster
-
specific for S-adenosyl-L-methionine
-
-
?
S-adenosyl-L-methionine + azathioprine
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + azathioprine
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + azathioprine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + azathioprine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
azathioprine is converted to mercaptopurine, which is subsequently metabolized through TPMT
-
-
?
S-adenosyl-L-methionine + azathioprine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
azathioprine is converted via a non-enzymatic reaction to mercaptopurine, which is subsequently metabolized through TPMT
-
-
?
S-adenosyl-L-methionine + azathioprine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
azathioprine is converted via a non-enzymatic reaction to mercaptopurine, which is subsequently metabolized through TPMT
-
-
?
S-adenosyl-L-methionine + azathioprine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
P51580
azathioprine is converted via a non-enzymatic reaction to mercaptopurine, which is subsequently metabolized through TPMT
-
-
?
S-adenosyl-L-methionine + mercaptopurine
S-adenosyl-L-homocysteine + methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thioguanine nucleotide
S-adenosyl-L-homocysteine + methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thioinosine monophosphate
S-adenosyl-L-homocysteine + methylthioinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thioinosine monophosphate
S-adenosyl-L-homocysteine + methylthioinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thioinosine triphosphate
S-adenosyl-L-homocysteine + methylthioinosine triphosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thiopurine
S-adenosyl-L-homocysteine + methylthiopurine
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
aliphatic thiol compounds are poor substrates or not methylated, dithiothreitol is no substrate
-
-
-
additional information
?
-
-
glutathione is no substrate
-
-
-
additional information
?
-
-
S-adenosyl-L-methionine and sinefungin prevent degradation of TPMT by stabilizing ist native structure
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiopurine
S-adenosyl-L-homocysteine + 6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
O55060
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
P51580
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
specific for S-adenosyl-L-methionine
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
enzyme plays an important role in metabolism of heterocyclic sulfhydryl drugs such as 6-thiopurine and 6-thioguanine
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
S-methylation, enzyme of major catabolic pathway of thiopurines
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
Mus musculus Swiss-Webster
-
specific for S-adenosyl-L-methionine
-
-
?
additional information
?
-
-
S-adenosyl-L-methionine and sinefungin prevent degradation of TPMT by stabilizing ist native structure
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
baseline activity 102%
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,3-Dithiopropanol
-
-
2,4-dithiopyrimidine
-
-
2,8-dihydroxy-6-mercaptopurine
-
-
2-Amino-6-thiopurine
-
-
2-Hydroxy-6-mercaptopurine
-
-
2-mercaptoethanol
-
-
2-methylthio-4-hydroxypyrimidine
-
1.8 mM, 45% inhibition
2-Methylthiouracil
-
-
3,4,5-triiodobenzoic acid
-
-
3,4-dimethoxy-5-hydroxybenzoic acid
-
-
3,4-dimethoxybenzoic acid
-
-
3,5-dichlorobenzoic acid
-
-
3,5-dihydroxy-4-methoxybenzoic acid
-
-
3,5-dimethylbenzoic acid
-
-
3,5-dinitrobenzoic acid
-
-
3-bromo-5-hydroxy-4-methoxybenzoic acid
-
-
3-chloro-5-hydroxy-4-methoxybenzoic acid
-
-
3-hydroxy-4,5-dimethoxybenzoic acid
-
-
3-hydroxy-4-methoxy-5-(dimethylamino)benzoic acid
-
-
3-hydroxy-4-methoxy-5-nitrobenzoic acid
-
-
3-hydroxy-4-methoxybenzoic acid
-
-
3-hydroxy-5-iodo-4-methoxybenzoic acid
-
-
4-hydroxy-3-methoxybenzoic acid
-
-
5-amino-salicylic acid
-
-
5-Aminosalicylate
-
-
5-methyl-2,4-dithiopyrimidine
-
-
6-hydroxy-2-thiopurine
-
-
6-Mercaptopurine
-
-
6-Mercaptopurine
-
TPMT activity and protein levels are diminished in cells incubated with 6-mercaptopurine
6-methylmercaptopurine
-
-
6-methylthiopurine
-
-
6-Thioguanine
-
mixed inhibitor of 6-mercaptopurine methylation
aspirin
-
-
Azathioprine
-
IC50: 0.43-0.532 mM
bendroflumethiazide
-
-
bendroflumethiazide
-
-
Benzoic acid
-
substituted benzoic acids, benzoic acid compounds, noncompetitive inhibition
Benzoic acid
-
benzoic acid derivatives
Benzoic acid
-
-
celecoxib
-
-
diclofenac
-
-
Disulfiram
-
-
Ethacrynic acid
-
-
Flurbiprofen
-
-
Furosemide
-
-
Furosemide
-
IC50: 0.015-0.019 mM, has the potential to inhibit thiopurine S-methyltransferase in patients with chronic inflammatory bowel disease
Furosemide
-
-
glutathione
-
-
glutathione
-
-
Ibuprofen
-
-
Ketoprofen
-
-
L-cysteine
-
1.8 mM, 50% inhibition
L-homocysteine thiolactone
-
-
lornoxicam
-
-
Mefenamic acid
-
-
meloxicam
-
-
mesalazine
-
-
N-ethylmaleimide
-
-
nabumetone
-
-
Naproxen
-
-
olsalazine
-
-
olsalazine
-
-
paracetamol
-
-
piretanide
-
IC50: 0.3-0.313 mM
piroxicam
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-methionine
-
-
S-Methylglutathione
-
-
sulfasalazine
-
-
sulfasalazine
-
-
Sulphasalazine
-
-
testosterone
-
; IC50: 0.03-0.072 mM
tolfenamic acid
-
-
trichlormethiazide
-
-
trichlormethiazide
-
-
tropolone
-
-
mesalazine
-
-
additional information
-
low levels of methionine can result in low S-adenosyl-L-methionine levels and consequently decreased TPMT activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S-adenosyl-L-methionine
-
S-adenosyl-L-methionine acts as a positive modulator of TPMT activity, the effect of S-adenosyl-L-methionine appears to be restricted to protein stabilisation rather than an increase of TPMT expression
SKF-525A
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
168
2-mercaptoethanol
-
-
1.7
2-Thiouracil
-
-
2
2-Thiouracil
-
-
0.138
6-hydroxy-8-mercaptopurine
-
-
0.00035
6-Mercaptopurine
O55060
-
0.00068
6-Mercaptopurine
-
wild-type
0.00091
6-Mercaptopurine
-
mutant R226H
0.0012
6-Mercaptopurine
-
mutant R226E
0.00143
6-Mercaptopurine
-
mutant R152H
0.00161
6-Mercaptopurine
-
mutant R226A
0.00273
6-Mercaptopurine
-
mutant R152A
0.00463
6-Mercaptopurine
-
mutant R152E
0.00632
6-Mercaptopurine
-
mutant R152A/R226A
0.0106
6-Mercaptopurine
-
recombinant enzyme, expressed in yeast
0.156
6-Mercaptopurine
-
-
0.224
6-Mercaptopurine
-
isoenzyme II
0.29
6-Mercaptopurine
-
cell lysate
0.3
6-Mercaptopurine
-
-
0.307
6-Mercaptopurine
-
isoenzyme I
0.32
6-Mercaptopurine
-
-
0.38
6-Mercaptopurine
-
kidney enzyme
0.383
6-Mercaptopurine
-
-
0.54
6-Mercaptopurine
-
erythrocyte
0.58
6-Mercaptopurine
-
-
0.58
6-Mercaptopurine
-
liver enzyme
0.65
6-Mercaptopurine
-
Molt-F4 cell
0.85
6-Mercaptopurine
-
peripheral blood mononuclear cell
0.99
6-Mercaptopurine
-
recombinant enzyme, baculovirus expressed
1.17
6-mercaptopurine-riboside
-
-
1.27
6-mercaptopurine-riboside-5'-monophosphate
-
-
0.89
6-mercaptopurine-riboside-5'-triphosphate
-
-
0.139
6-selenoguanine-riboside
-
-
0.0291
6-selenopurine
-
-
0.0518
6-selenopurine-riboside
-
-
0.1314
6-thiodeoxyguanosine
-
recombinant enzyme, expressed in yeast
0.0127
6-thiodeoxyinosine
-
recombinant enzyme, expressed in yeast
0.0137
6-Thioguanine
-
mutant L69V, cytosolic fraction of yeast cells is incubated with 500 microM of 6-TG and 0-400 microM of SAM
0.0152
6-Thioguanine
P51580
-
0.0181
6-Thioguanine
-
recombinant enzyme, expressed in yeast
0.0188
6-Thioguanine
P51580
1.2fold increase in KM-value compared to wild-type variant
0.03435
6-Thioguanine
-
wild-type enzyme, cytosolic fraction of yeast cells is incubated with 500 microM of 6-TG and 0-400 microM of SAM
0.0349
6-Thioguanine
-
-
0.0448
6-Thioguanine
P51580
2.9fold increase in KM-value compared to wild-type variant
0.0555
6-Thioguanine
-
the Km-value of the variant Ser125Leu is 1.6fold higher than the Km-value of the wild-type variant, the ratio of Vmax to Km-value is 27% of the wild-type ratio
0.056
6-Thioguanine
-
mutant R215H, variant TPMT*8
0.0562
6-Thioguanine
-
mutant L69V, cytosolic fraction of yeast cells is incubated with 0-350 microM of 6-TG and 1mM of SAM
0.0627
6-Thioguanine
-
wild-type enzyme, cytosolic fraction of yeast cells is incubated with 0-350 microM of 6-TG and 1mM of SAM
0.0635
6-Thioguanine
-
the Km-value of the variant Gly144Arg is 1.8fold higher than the Km-value of the wild-type variant, the ratio of Vmax to Km-value is 31% of the wild-type ratio
0.072
6-Thioguanine
-
mutant C212R, cytosolic fraction of yeast cells is incubated with 0-350 microM of 6-TG and 1mM of SAM
0.0759
6-Thioguanine
-
the Km-value of the variant Glu28Val is 2.2fold higher than the Km-value of the wild-type variant, the ratio of Vmax to KM-value is 58% of the wild-type ratio
0.076
6-Thioguanine
-
mutant K119T, variant TPMT*9
0.07985
6-Thioguanine
-
mutant K119T, cytosolic fraction of yeast cells is incubated with 0-350 microM of 6-TG and 1mM of SAM
0.08
6-Thioguanine
-
wild-type, variant TPMT*1
0.08305
6-Thioguanine
-
mutant Q179H, cytosolic fraction of yeast cells is incubated with 0-350 microM of 6-TG and 1mM of SAM
0.098
6-Thioguanine
-
mutant A167G, variant TPMT*23
0.125
6-Thioguanine
-
mutant G144R, variant TPMT*10
0.127
6-Thioguanine
-
mutant S125L, variant TPMT*12
0.13
6-Thioguanine
-
-
0.151
6-Thioguanine
-
mutant A80P, variant TPMT*2
0.156
6-Thioguanine
-
mutant Y240C, variant TPMT*3C
0.1799
6-Thioguanine
-
the Km-value of the variant Gly144Arg is 5.1fold higher than the Km-value of the wild-type variant, the ratio of Vmax to KM-value is 10.4% of the wild-type ratio
0.186
6-Thioguanine
-
mutant K122T, variant TPMT*19
0.353
6-Thioguanine
-
mutant K238E, variant TPMT*20
0.485
6-Thioguanine
-
mutant Y180F, variant TPMT*6
0.55
6-Thioguanine
-
-
0.55
6-Thioguanine
-
mutant E28V, variant TPMT*13
0.557
6-Thioguanine
-
-
0.6
6-Thioguanine
-
mutant R163H, variant TPMT*16
1.027
6-Thioguanine
-
mutant H227Q, variant TPMT*7
1.094
6-Thioguanine
-
mutant G36S, variant TPMT*24
1.267
6-Thioguanine
-
mutant Q42E, variant TPMT*17
1.45
6-Thioguanine
-
mutant C132Y, variant TPMT*11
0.761
6-thioguanine-riboside
-
-
1.04
6-thioguanine-riboside-5'-monophosphate
-
-
-
0.0261
6-thioguanosine
-
recombinant enzyme, expressed in yeast
0.0271
6-thioguanosine 5-monophosphate
-
recombinant enzyme, expressed in yeast
0.0551
6-thioinosine
-
recombinant enzyme, expressed in yeast
0.0257
6-thioinosine 5'-monophosphate
-
recombinant enzyme, expressed in yeast
0.2
6-Thiopurine
-
-
0.231
7-methyl-6-mercaptourine
-
-
-
0.0961
8-hydroxy-6-mercaptopurine
-
-
0.292
9-(n-butyl)6-mercaptopurine
-
-
0.159
9-(n-propyl)-6-thioguanine
-
-
0.0024
S-adenosyl-L-methionine
-
cell lysate
0.0027
S-adenosyl-L-methionine
-
-
0.0056
S-adenosyl-L-methionine
O55060
-
0.00637
S-adenosyl-L-methionine
-
isoenzyme II
0.00665
S-adenosyl-L-methionine
-
Molt-F4 cell
0.00722
S-adenosyl-L-methionine
-
isoenzyme I
0.0119
S-adenosyl-L-methionine
-
erythrocyte
0.0148
S-adenosyl-L-methionine
-
mutant R226E
0.0164
S-adenosyl-L-methionine
-
peripheral blood mononuclear cell
0.0185
S-adenosyl-L-methionine
-
wild-type
0.0197
S-adenosyl-L-methionine
-
mutant R226A
0.0199
S-adenosyl-L-methionine
-
mutant R226H
0.0237
S-adenosyl-L-methionine
-
mutant R152H
0.0254
S-adenosyl-L-methionine
-
mutant R152A
0.0445
S-adenosyl-L-methionine
-
mutant R152E
0.0463
S-adenosyl-L-methionine
-
mutant R152A/R226A
0.372
9-ethyl-6-mercaptopurine
-
-
additional information
additional information
-
various thiophenols as substrates, Km 0.0008-0.0078
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.027
2-Hydroxy-6-mercaptopurine
-
-
0.01
3,4-dimethoxy-5-hydroxybenzoic acid
-
-
0.0107
3,4-dimethoxy-5-hydroxybenzoic acid
-
isoenzyme II
0.0113
3,4-dimethoxy-5-hydroxybenzoic acid
-
isoenzyme I
0.00802
6-Mercaptopurine
-
isoenzyme II
0.0113
6-Mercaptopurine
-
isoenzyme I
0.45
6-Thioguanine
-
-
0.9
6-Thioguanine
-
-
2.413
celecoxib
-
-
0.722
diclofenac
-
-
1.524
Flurbiprofen
-
-
1.043
Ibuprofen
-
-
0.172
Ketoprofen
-
-
1.41
lornoxicam
-
-
0.039
Mefenamic acid
-
-
4.238
meloxicam
-
-
4.3
nabumetone
-
-
0.052
Naproxen
-
-
0.208
olsalazine
-
-
5.162
paracetamol
-
-
2.589
piroxicam
-
-
0.00075
S-adenosyl-L-homocysteine
-
-
0.05
tolfenamic acid
-
-
0.85
tropolone
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.43 - 0.532
Azathioprine
-
IC50: 0.43-0.532 mM
2.416
celecoxib
-
-
1.582
diclofenac
-
-
1.649
Flurbiprofen
-
-
0.015 - 0.019
Furosemide
-
IC50: 0.015-0.019 mM, has the potential to inhibit thiopurine S-methyltransferase in patients with chronic inflammatory bowel disease
1.968
Ibuprofen
-
-
1.013
Ketoprofen
-
-
2.135
lornoxicam
-
-
0.039
Mefenamic acid
-
-
4.292
meloxicam
-
-
4.341
nabumetone
-
-
0.079
Naproxen
-
-
1.474
olsalazine
-
-
5.168
paracetamol
-
-
0.3 - 0.313
piretanide
-
IC50: 0.3-0.313 mM
2.589
piroxicam
-
-
0.03 - 0.072
testosterone
-
IC50: 0.03-0.072 mM
0.063
tolfenamic acid
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00000716
-
TMPT reference activity after recovery of the bone marrow suppression
0.00003033
-
elevated TPMT activity during the recovery phase of a bone marrow suppression, following the pancytopenic period
1.03
-
-
additional information
-
determination of thiopurine S-methyltransferase activity in erythrocytes using 6-thioguanine as substrate and a non-extraction liquid chromatographic technique. This method minimzes sample-handling, reduces inherent imprecision, the possibility of laboratory error and has a potential for further automation
additional information
-
normal thiopurine methyltransferase activity, 7.5-14 U/ml erythrocytes
additional information
-
the median activity of TPMT is 44.7 ng/ml/h
additional information
-
TPMT activity amongst 253 healthy Estonian volunteers varies from 21.5 ng/ml/h to 185.5 ng/ml/h with a median of 86.24 ng/ml/h
additional information
-
TPMT activity of 0.5% of the patients is low, less than 5 U/ml RBC, for 11.9% intermediate, 5-13.7 U/ml RBC, and for 87.6% high, greater than 13.7 U/ml RBC
additional information
-
median TPMT activities, Singapore Chinese 16.4 U, Singapore Malays 17.8 U, Singapore Indians 16.4 U, one unit of activity is defined as a formation of 1 nmol of 6-methylmercaptopurine per ml of packed red blood cells per h incubation at 37C
additional information
-
activity of TPMT in nmol of the formed 6-mMP/g Hb/h, dialyzed patients, total 30.6, females 30.1, males 31.7, control group, total 28.4, females 28.4, males 28.7
additional information
-
thiopurine methyltransferase levels above 23 nmol 6-methylthioguanine/g Hb per h indicates normal enzyme activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
-
TPMT activity assay
6.5
O55060
TPMT activity assay
7.4
-
6-thioguanine S-methylation assay
7.4
-
TPMT activity assay
7.4
-
enzyme assay of thiopurine S-methyltransferase activity in COS-7 cells
7.5
-
TPMT activity assay
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.5 - 8.6
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
6-thioguanine S-methylation assay
37
-
TPMT activity assay
37
O55060
TPMT activity assay
37
-
TPMT activity assay
37
-
TPMT activity assay
37
-
enzyme assay of thiopurine S-methyltransferase activity in COS-7 cells
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
primary cell
Manually annotated by BRENDA team
-
embryonic kidney cell line with inducible thiopurine methyltransferase
Manually annotated by BRENDA team
-
from patients with chronic inflammatory bowel disease
Manually annotated by BRENDA team
-
TPMT activity is significantly lower in patients with acute lymphoblastic leukemia compared to control. Increase of TPMT activity during maintainance treatment with 6-mercaptopurine and already after induction therapy (treatment with antifolates, e.g. methotrexate and trimethoprim), before the patients receive 6-mercaptopurine
Manually annotated by BRENDA team
-
TPMT phenotyping
Manually annotated by BRENDA team
Mus musculus Swiss-Webster
-
-
-
Manually annotated by BRENDA team
-
peripheral blood leukocytes
Manually annotated by BRENDA team
-
TPMT genotyping
Manually annotated by BRENDA team
Mus musculus Swiss-Webster
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28000
-
-
485522, 485526, 686157
30000
-
2 isozymes, gel filtration
485519
33000
-
determined by SDS-PAGE and immunoblotting
685039
35000
-
-
686275
36000
-
gel filtration
485516
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 35000, SDS-PAGE
monomer
-
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
two crystal structures of murine TPMT are determined, as a binary complex with the product S-adenosyl-L-homocysteine and as a ternary complex with S-adenosyl-L-homocysteine and the substrate 6-mercaptopurine, to 1.8 and 2.0 A resolution, respectively
O55060
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45 - 56
-
heat inactivation, 23% of the activity is lost after 20 min at 45C, 95% activity is lost after 6 min at 56C
485515
55
-
the melting temperature of the wild type enzyme is at 55C
718942
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine is responsible for direct stabilization of the enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
80C, activity in cell lysate is stable during storage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 isozymes
-
cytosolic fractions of transformed Saccharomyces cerevisiae cells are prepared
-
Ni-NTA column chromatography and Superdex 200 gel filtration
-
using a Ni2+-NTA resin and a gel-filtration column
-
using a Ni2+-NTA resin and a gel-filtration column
O55060
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
baculovirus expressed
-
cDNA cloning, heterologous expression in yeast
-
enhanced green fluorescent protein-tagged enzyme is expressed in Escherichia coli, Jurkat, Hep-G2, and HEK-293 cells
-
expressed in COS-1 cells
-
expressed in Escherichia coli BL21-Codon Plus (DE3)-RIL cells
-
for cloning of the TPMT fragment the TOPO TA cloning kit is used
-
into the pCR2.1-TOPO vector, used as a template to generate point mutations, the variants are sequenced and cloned into the mammalian expression vector pCMV6-XL5, into the pENTR/D-TOPO vector and subsequently into the pcDNA-DEST40 vector
-
into the yeast expression vector pYeDP60 for transformation of Saccharomyces cerevisiae cells
-
retroviral gene transfer
-
the full-length coding region is amplified by PCR from a eukaryotic expression plasmid and cloned into the pET-28a vector for expression in Escherichia coli BL21DE3 cells
-
to assess the functional effect of the trinucleotide repeat variants in the promoter, the wild-type and variant TPMT promoters are amplified and cloned into the promoter-less pGL3-Basic vector
-
a 8.7 kb fragment encompassing part of exon III through a portion of intron 6 is subcloned into the pZERO-2 vector
-
cDNA cloned and heterologous expressed in rabbit reticulocytes and wheat germ lysate
O55060
the full-length coding region is amplified by PCR from a eukaryotic expression plasmid and cloned into the pET-28a vector for expression in Escherichia coli BL21DE3 cells
O55060
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decreased activity of TPMT is associated with hematopoietic toxicity after administration of standard doses of 6- mercaptopurine or azathioprine
-
the restriction of L-methionine in cell growth media reversibly decreases enzyme activity and protein levels
-
S-adenosyl-L-methionine has no effect on TPMT mRNA expression
-
azathioprine therapy can raise TPMT activity
-
longitudinal induction of thiopurine methyltransferase activity is observed during 6-thioguanine treatment
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smokers have significantly higher TPMT activity than nonsmokers
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TPMT activity is significantly higher in wild type children than in wild type adults (18-68 years), wild type infants from 0.08-5 years has a 9% higher average TPMT activity than the other wild type groups, only in children from 0.08-2 years is the TPMT activity higher in males than in females
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
238G>C
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TPMT variant
238G>C
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TPMT variant, inactivating mutation in exon 5
460G>A
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TPMT variant
460G>A
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TPMT variant, inactivating mutation in exon 7
460G>A/719A>G
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TPMT*3A polymorphism, low or no TPMT activity
539A>T
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TPMT variant
719A>G
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TPMT variant
719A>G
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TPMT variant, inactivating mutation in exon 10
A154T
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460G>A sequence variant of the TPMT gene, location exon 7, amino acid change A154T
A154T
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polymorphism TPMT*3B
A154T
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polymorphism TPMT*3B, single nucleotide substitution G460A
A154T
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variant TPMT*3B
A154T
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variant TPMT*3B, G460A polymorphismus
A154T
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mutant shows decreased TPMT activity
A154T
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the mutation affects TMPT activity
A154T/Y240C
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mutant with reduced activity
A154T/Y240C
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polymorphism TPMT*3A
A154T/Y240C
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polymorphism TPMT*3A, single nucleotide substitutions G460A and A719G
A154T/Y240C
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TPMT*3A polymorphismus
A154T/Y240C
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variant TPMT*3A
A154T/Y240C
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mutant shows decreased TPMT activity
A154Y
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thiopurine S-methyltransferase polymorphism, G to A transition at position 460
A167G
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variant TPMT*23
A167G
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mutant shows decreased TPMT activity
A167G
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the mutation affects TMPT activity
A180P
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the mutation affects TMPT activity
A80P
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mutant with reduced activity
A80P
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238G>C sequence variant of the TPMT gene, location exon 5, amino acid change A80P
A80P
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polymorphism TPMT*2
A80P
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polymorphism TPMT*2, single nucleotide substitution G238C
A80P
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thiopurine S-methyltransferase polymorphism, G to C transition at position 238
A80P
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TPMT*2 polymorphismus
A80P
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variant TPMT*2
A80P
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mutant shows decreased TPMT activity
A80P
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the mutant is substantially destabilized and shows 47% of wild type activity
C132Y
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variant TPMT*11
C132Y
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mutant shows decreased TPMT activity
C132Y
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the mutation affects TMPT activity
C212R
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polymorphism c.634T>C, TPMT*25
C212R
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mutant shows decreased TPMT activity
E28V
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variant TPMT*13
E28V
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mutant shows decreased TPMT activity
E28V
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the mutation affects TMPT activity
E98X
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the mutation affects TMPT activity
F208L
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the mutation is associated with a decrease in enzyme activity
G144R
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variant TPMT*10
G144R
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mutant shows decreased TPMT activity
G144R
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the mutation affects TMPT activity
G36S
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variant TPMT*24
G36S
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mutant shows decreased TPMT activity
G71R
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variant TPMT*18
G71R
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mutant shows decreased TPMT activity
G71R
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the mutation affects TMPT activity
H227Q
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variant TPMT*7
H227Q
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mutant shows decreased TPMT activity
H227Q
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the mutation affects TMPT activity
K119T
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356A>C sequence variant of the TPMT gene, location exon 5, amino acid change K119T
K119T
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polymorphism c.356A>C, TPMT*9
K119T
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variant TPMT*9
K119T
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mutant shows decreased TPMT activity
K119T
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the mutation affects TMPT activity
K122T
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variant TPMT*19
K122T
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mutant shows normal TPMT activity
K238E
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variant TPMT*20
K238E
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mutant shows decreased TPMT activity
K238E
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the mutation affects TMPT activity
L49S
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variant TPMT*5
L49S
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mutant shows decreased TPMT activity
L49S
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the mutation affects TMPT activity
L49S
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the mutant shows much greater stability comparable to that of wild type enzyme and exhibits 14% of wild type activity
L69V
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polymorphism c.205C>G, TPMT*21
L69V
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variant TPMT*21
L69V
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mutant shows decreased TPMT activity
L69V
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the mutation affects TMPT activity
M1V
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variant TPMT*14
Q179H
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polymorphism c.537G>T, TPMT*24
Q42E
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variant TPMT*17
Q42E
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mutant shows decreased TPMT activity
Q42E
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the mutation affects TMPT activity
R152A
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mutant to probe, whether this residue is important for catalysis
R152A/R226A
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mutant to probe, whether this residue is important for catalysis
R152E
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mutant to probe, whether this residue is important for catalysis
R152H
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mutant to probe, whether this residue is important for catalysis
R163H
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variant TPMT*16
R163H
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mutant shows decreased TPMT activity
R163H
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the mutation affects TMPT activity
R163P
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variant TPMT*22
R163P
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mutant shows decreased TPMT activity
R163P
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the mutation affects TMPT activity
R215H
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variant TPMT*8
R215H
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mutant shows decreased TPMT activity
R215H
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the mutation affects TMPT activity
R226A
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mutant to probe, whether this residue is important for catalysis
R226E
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mutant to probe, whether this residue is important for catalysis
R226H
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mutant to probe, whether this residue is important for catalysis
S125L
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374C>T sequence variant of the TPMT gene, location exon 6, amino acid change S125L
S125L
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variant TPMT*12
S125L
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mutant shows decreased TPMT activity
S125L
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the mutation affects TMPT activity
TPMT*2
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polymorphism, single nucleotide substitution G238C
TPMT*2
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polymorphism, single nucleotide substitution G238C, inactivating mutation
TPMT*2
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polymorphism, single nucleotide substitution, G238C at codon 80
TPMT*23
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polymorphism, single nucleotide substitution, C500G
TPMT*3A
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polymorphism, single nucleotide substitutions G460A and A719G
TPMT*3A
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polymorphism, single nucleotide substitutions, G460A and A719G
TPMT*3A
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polymorphism, single nucleotide substitutions, G460A at codon 154 and A719G at codon 240
TPMT*3B
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polymorphism, single nucleotide substitution G460A
TPMT*3B
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polymorphism, single nucleotide substitution G460A, inactivating mutation
TPMT*3B
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polymorphism, single nucleotide substitution, G460A at codon 154
TPMT*3C
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polymorphism, single nucleotide substitution A719G
TPMT*3C
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polymorphism, single nucleotide substitution A719G, inactivating mutation
TPMT*3C
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polymorphism, single nucleotide substitution, A719G at codon 240
Y107D
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the mutant shows less than 10% activity compared to the wild type enzyme, the variant allozyme shows a striking decrease in both immunoreactive protein level and enzyme activity after transient expression in COS-1 cells, the mutant is less stable than the wild type TPMT allozyme
Y180F
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variant TPMT*6
Y180F
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mutant shows decreased TPMT activity
Y180F
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the mutation affects TMPT activity
Y240C
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719A>G sequence variant of the TPMT gene, location exon 10, amino acid change Y240C
Y240C
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polymorphism TPMT*3C
Y240C
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polymorphism TPMT*3C, single nucleotide substitution A719G
Y240C
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thiopurine S-methyltransferase polymorphism, A to G transition at position 719
Y240C
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TPMT*3C polymorphismus
Y240C
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variant TPMT*3C
Y240C
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variant TPMT*3C, A719G polymorphismus
Y240C
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mutant shows decreased TPMT activity
Y240C
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the mutation affects TMPT activity
A154T
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polymorphism TPMT*3B
A154T/Y240C
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polymorphism TPMT*3A
A154T/Y240C/E98STOP
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polymorphism TPMT*3D
A80P
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polymorphism TPMT*2
C132Y
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polymorphism TPMT*11
E28V
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polymorphism TPMT*13
G144R
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polymorphism TPMT*10
G36S/K238E
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polymorphism TPMT*20
G71R
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polymorphism TPMT*18
H227E
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polymorphism TPMT*7
K122T
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polymorphism TPMT*19
L49S
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polymorphism TPMT*5
Q42E
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polymorphism TPMT*17
R163H
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polymorphism TPMT*16
R163P
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polymorphism TPMT*22
R215H
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polymorphism TPMT*8
S125L
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polymorphism TPMT*12
Y180F
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polymorphism TPMT*6
Y240C
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polymorphism TPMT*3C
M1V
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the mutation affects TMPT activity
additional information
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at least 23 single nucleotide polymorphisms in the TPMT gene have been identified that are associated with decreased or absent TPMT activity
additional information
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genetic polymorphisms of thiopurine methyltransferase are responsible for the variable expression of enzyme activity translating into variable efficacy and toxicity
additional information
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more than 20 variant alleles leading to deficient methylation phenotype have been described, four of them, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C, account for 80-95% of low activity alleles in various populations
additional information
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PCR amplification generates a DNA fragment of 197 bp spanning the TPMT*2, 12225G>C transversion, polymorphism
L69V
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polymorphism TPMT*21
additional information
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no amino acid substitutions in the polymorphisms TPMT*4 and TPMT*15, Met-Val substitution in the start codon of TPMT*14
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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the goal is to determine which metabolite of azathioprine has the most antiviral activity and to gain a better understanding of how this compound may act in vitro
analysis
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determination of thiopurine S-methyltransferase activity in erythrocytes using 6-thioguanine as substrate and a non-extraction liquid chromatographic technique. This method minimzes sample-handling, reduces inherent imprecision, the possibility of laboratory error and with the potential for further automation, makes it ideal for use in a regional refferal laboratory
analysis
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monitoring of 6-thiopurine S-methyltransferase activity is especially important when patients are treated with 6-thiopurine drugs (drugs in treatment of acute lymphoblastic leukemia), since severe bone marrow toxicity may be induced if patients have deficient 6-thiopurine S-methyltransferase activity. The HPLC-based method enables the rapid screening of 6-6-thiopurine S-methyltransferase activities in patients treated with 6-thiopurines
analysis
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monitoring of TPMT activity may be of benefit to improve thiopurine therapy
diagnostics
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the chip-based miniaturization provides a clinically feasible genotyping platform for one-at-a-time testing
diagnostics
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thiopurine S-methyltransferase genotypes or phenotypes may be a predictive factor for azathioprine-induced toxicities
medicine
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enzyme may be a target for clinically significant drug interactions, the common genetic polymorphism might be a risk factor for the occurence of therapy-dependent secondary leukemia
medicine
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enzyme activity might represent one factor responsible for variations in the therapeutic or toxic effects of thiopurine and thiopyrimidine drugs used clinically to treat recipients of transplanted kidneys and patients with renal disease such as glomerulonephritis
medicine
P51580
identification of a novel non-functional allele of the thiopurine S-methyltransferase gene enhances the efficiency of genotyping methods to predict patients at risk of an inadequate response to thiopurine therapy
medicine
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the knowledge of the genetic basis of interindividual variability in thiopurine S-methyltransferase activity could enhance the efficiency of genotyping methods to preduct patients at risk of inadequate response to thiopurine therapy, the knowledge of the genetic basis of interindividual variability in thiopurine S-methyltransferase activity could enhance the efficiency of genotyping methods to product patients at risk of inadequate response to thiopurine therapy
medicine
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azathioprine sodium is a purine antagonist commonly used as an adjuvant immunosuppressive agent in treating Pemphigus Vulgaris, mercaptopurine is the active compound, TPMT is the principal inactivation enzyme for this cytotoxic metabolite in hematopoietic tissues
medicine
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detecting TPMT genetic variants before the administration of azathioprine has the potential to prevent serious and costly adverse drug reactions, such as neutropenia
medicine
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evaluation of a possible long-term effect of mesalazine or azathioprine on thiopurine methyltransferase activity is of particular clinical importance because both drugs can to be given for several years in inflammatory bowel disease
medicine
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first case of azathioprine-associated AML linked to low thiopurine S-methyltransferase enzyme activity
medicine
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genetic variation in thiopurine S-methyltransferase is a major factor for wide variation in the metabolism and safety of thiopurine drugs
medicine
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genotyping at diagnosis identifies patients with a homozygous mutant TPMT and may prevent severe and life-threatening toxicity, ALL treatment monitoring should preferentially be based on repeated determinations of intracellular active metabolites, 6-TGN, and methylated metabolites
medicine
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individuals with decreased TPMT activity are at great risk for adverse reactions if treated with conventional thiopurine doses
medicine
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individuals with decreased TPMT activity are at high risk of fatal adverse reactions if treated with conventional thiopurine doses
medicine
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myelosuppression occurs in 2-7% of inflammatory bowel disease patients treated with azothioprine, and can be associated with reduced activity of thiopurine methyltransferase in some patients
medicine
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patients carrying a variant genotype have low TPMT activity and produce elevated levels of 6-thioguanine nucleotides in their red blood cells, 6-TGN accumulation may result in azathioprine-induced bone marrow myelosuppression in the course of treatment with the drug in a standard dosage regimen in patients following renal transplantation
medicine
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patients carrying defective mutations in TMPT gene have elevated thioguanine nucleotides concentrations that finally result in severe or even fatal hematopoietic toxicities when they are treated with standard doses of 6-mercaptopurine
medicine
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patients with inflammatory bowel disease may have different thiopurine dose requirements in relation to thiopurine methyltransferase genotype or phenotype
medicine
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polymorphisms at the thiopurine S-methyltransferase coding gene determine enzyme activity and consequently, the development of toxicity secondary to thiopurines
medicine
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single nucleotide polymorphisms are known to be responsible for variations in the metabolism of numerous drugs in humans, thiopurine S-methyltransferase displays polymorphisms with varying prevalence among different populations
medicine
-
the goal is to determine which metabolite of azathioprine has the most antiviral activity and to gain a better understanding of how this compound may act in vitro
medicine
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the knowledge of the TPMT activity distribution in each population seems relevant, the incidence of hematologic adverse effects associated with azathioprine and 6-mercaptopurine treatment probably depends on that distribution
medicine
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the remarkable change in enzyme activity of TPMT may be explained by differences in the age of red blood cells, as younger erythrocytes have a higher TPMT activity
medicine
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the results suggest that coadministration of thiopurines and various nonsteriodal anti-inflammatory drugs may lead to drug interactions
medicine
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the use of azothioprine and mercaptopurine is limited by toxicity, especially myelosuppression, which is related to activity of the enzyme thiopurine S-methyltransferase
medicine
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thiopurine methyltransferase activity inversely correlated with clinical response to thiopurine treatment in inflammatory bowel disease
medicine
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thiopurine methyltransferase is a genetically moderated key enzyme involved in the metabolism of azathioprine that can be used to stratify individuals into different levels of risk of developing neutropaenia
medicine
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thiopurine methyltransferase is the main enzyme responsible for inactivating toxic products of azathioprine metabolism
medicine
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thiopurine methyltransferase metabolises thiopurine drugs and influences their cytotoxic activity
medicine
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thiopurine S-methyltransferase activity is inversely related to the risk of developing severe hematopoietic toxicity in patients treated with azathioprine
medicine
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thiopurine S-methyltransferase is a key enzyme in the detoxification of thiopurine drugs widely used in the treatment of various diseases, such as inflammatory bowel diseases, acute lymphoblastic leukaemia and rheumatic diseases
medicine
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thiopurine S-methyltransferase is an enzyme responsible for the detoxification of the widely used thiopurine drugs
medicine
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thiopurine S-methyltransferase modulates the cytotoxic effects of thiopurine prodrugs such as 6-mercaptopurine by methylating them in a reaction using S-adenosyl-L-methionine as the donor
medicine
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while factors other than TPMT status are likely to be involved in azathioprine toxicity, the majority of evidence suggests that TPMT deficiency is a significant independent risk factor for myelotoxicity
medicine
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determination of TPMT and monitoring of thiopurine metabolites allows azathioprine treatment to be optimised
medicine
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induction of thiopurine methyltransferase is associated with recalcitrant disease
medicine
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mercaptopurine dose can be adjusted on the basis of TPMT genotype to mitigate toxicity in pediatric patients with acute lymphoblastic leukemia
medicine
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TPMT activity is a good prediction factor for the toxicity and efficacy of the antileukemic thiopurine therapy
medicine
-
low enzyme level can lead to greater sensitivity to thiopurine therapy in astroglial cells
medicine
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thiopurine S-methyltransferase gene polymorphisms are pharmacogenetic markers which enable the individualization of thiopurine drug therapy
medicine
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the murine model recapitulates many clinical features of the human polymorphism and provides a preclinical system for establishing safer regimens of genetically influenced antileukemic drug therapy
medicine
O55060
thiopurine S-methyltransferase modulates the cytotoxic effects of thiopurine prodrugs such as 6-mercaptopurine by methylating them in a reaction using S-adenosyl-L-methionine as the donor
medicine
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low enzyme level can lead to greater sensitivity to thiopurine therapy in astroglial cells