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Thiopurine methyltransferase in humans: development and tissue distribution.

Thiopurine methyltransferase (EC 2.1.1.67, TPMT) was studied with 6-mercaptopurine as substrate in the cytosolic fraction from 18 human fetal liver, 16 placental and 22 adult liver specimens. TPMT activity (pmol x min-1 x mg-1; mean +/- SD) was 33.2 +/- 15.8 (fetal liver), 19.5 +/- 11.1 (placenta) and 105 +/- 57.1 (adult liver). Fetal liver activity of TPMT is one third that in adult liver suggesting that this enzyme is well developed in the mid-gestational human fetus. The distribution of TPMT seems to be ubiquitous both in the fetus and adult subject. The kidney is an important site of methylation as suggested by the renal activity of TPMT (197 +/- 70 pmol x min-1 x mg-1) which is twice as high as the hepatic one. Fetal and adult hepatic TPMT obey nonmichaelian kinetics. Two phases, one with lower and one with higher affinity for 6-mercaptopurine, were observed. The average Km for the high affinity phase was 0.12 mmol/l (fetus) and 0.13 mmol/l (adult), whereas the Km for the lower affinity phase was 1.79 mmol/l (fetus) and 1.42 mmol/l (adult). This paper shows that TPMT develops before the second trimester of gestation in human fetus, that it has an ubiquitous distribution in the human fetus and adult subjects and the kinetic pattern of this enzyme is consistent in fetal and adult liver.