THIOPURINE METHYLTRANSFERASE IN HUMANS - DEVELOPMENT AND TISSUE DISTRIBUTION

Thiopurine methyltransferase (EC 2.1.1.67, TPMT) was studied with 6-me rcaptopurine as substrate in the cytosolic fraction from 18 human feta l liver, 16 placental and 22 adult liver specimens. TPMT activity (pmo l 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 activit y of TPMT is one third that in adult liver suggesting that this enzyme is well developed in the midgestational human fetus. The distribution of TPMT seems to be ubiquitous both in the fetus and adult subject. T he kidney is an important site of methylation as suggested by the rena l 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 nonmichaeli an kinetics. Two phases, one with lower and one with higher affinity f or 6-mercaptopurine, were observed. The average K(m) for the high affi nity phase was 0.12 mmol/l (fetus) and 0.13 mmol/l (adult), whereas th e K(m) for the lower affinity phase was 1.79 mmol/l (fetus) and 1.42 m mol/l (adult). This paper shows that TPMT develops before the second t rimester of gestation in human fetus, that it has an ubiquitous distri bution in the human fetus and adult subjects and the kinetic pattern o f this enzyme is consistent in fetal and adult liver.