Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.67 (
thiopurine methyltransferase
)
551
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The indication for the determination of both
thiopurine methyltransferase
(
TPMT
) and inosine triphosphate pyrophosphohydrolase is identical (i.e., adverse drug reactions toward mercaptopurines). Therefore, we tested whether or not our standard procedure to prepare erythrocyte lysates for measurement of
TPMT
activity, which includes treatment with Chelex 100 (a chelating resin), was suitable for the measurement of
ITPase
activity. It also was tested to see if
ITPase
activity differs in EDTA and Heparin anti-coagulated blood samples. We found that there was no difference between the
ITPase
activity in erythrocyte lysates prepared from EDTA or Heparin anti-coagulated blood. Treatment with a chelating resin or omission of magnesium from the assay procedure resulted in decreased and nearly absent
ITPase
activity, respectively. We conclude that untreated erythrocyte lysates obtained for determination of
TPMT
activity are suitable for determination of
ITPase
activity. However, after treatment with Chelex 100 the erythrocyte lysates become unsuitable for determination of
ITPase
activity.
...
PMID:Determination of ITPase activity in erythrocyte lysates obtained for determination of TPMT activity. 1706 77
The thiopurine drugs-azathioprine (AZA), 6-mercaptopurine (6-MP), and thioguanine-are widely used to treat malignancies, rheumatic diseases, dermatologic conditions, inflammatory bowel disease, and solid organ transplant rejection. However, thiopurine drugs have a relatively narrow therapeutic index and are capable of causing life-threatening toxicity, most often myelosuppression. Thiopurine S-methyltransferase (
TPMT
;
EC 2.1.1.67
), an enzyme that catalyzes S-methylation of these drugs, exhibits a genetic polymorphism in 10% of Caucasians, with 1/300 individuals having complete deficiency. Patients with intermediate or deficient
TPMT
activity are at risk for excessive toxicity after receiving standard doses of thiopurine medications. This report reviews the recent advances in the knowledge of the mechanism of action as well as the molecular basis and interethnic variations of
TPMT
and inosine triphosphate pyrophosphatase (
ITPase
; EC 3.6.1.19), another enzyme implicated in thiopurine toxicity. In addition, an update on pharmacokinetics, metabolism, drug-drug interactions, safety, and tolerability of thiopurine drugs is provided.
...
PMID:Clinical pharmacology and pharmacogenetics of thiopurines. 1850 37
