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Methylation is the major biotransformation route of thiopurine drugs such as 6-mercaptopurine (6MP), used in the treatment of inflammatory diseases such as rheumatoid arthritis and childhood acute lymphoblastic leukemia. 6MP and it's thioguanine nucleotide metabolites are principally inactivated by thiopurine methyltransferase (TPMT)-catalyzed S-methylation. <br>TPMT exhibits an autosomal co-dominant trait: About one in 300 Caucasian, African, African-American, and Asian populations are TPMT deficient. Approximately 6-10% of these populations inherit intermediate TPMT activity and are heterozygous at the TPMT locus. The rest are homozygous for the wild-type allele and have high levels of TPMT activity. Low or undetectable levels of TPMT results in patients having this trait being at risk to thiopurine drug-induced toxicity such as myelosuppression.<br>6-MP is a typical substrate for TPMT as shown in this example., Reviewed: D'Eustachio, P, 2008-05-28 08:30:54
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6-mercaptopurine can be S-methylated
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2.1.1.67
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