Human fetal and adult liver was found to catalyze the metabolism of a glutathione conjugate, acetaminophen-glutathione, to the cysteine conjugate. The activity was higher in the fetal than in the adult liver, 4.06 ± 0.59 arid 1.63 ± 0.42 nmol/10 min/mg protein, respectively. The initial reaction was catalyzed by ,-glutamyltransferase, as indicated by the inhibitory effect of serine-borate. The hydrolysis of the formed cysteinylglycine conjugate was extremely rapid since no such conjugate was detected and an almost stoichiometric formation of acetaminophen-cysteine from acetaminophen-glutathione was observed. The human fetal kidney also metabolized acetaminophen-glutathione to the corresponding conjugate. This activity was, however, lower than in the liver from the same fetus.

Glucuronidation of harmol in microsomal preparations and sulphate conjugation in hepatic 105,000 g supernatant fractions were studied comparatively in human fetal and adult liver subcellular preparations. The formation of harmol sulphate in the fetal liver was slightly lower than in the adult liver and considerably lower than in rat liver. No glucuronidation of harmol was found in fetal liver, while the activity in adult liver was 30-80 nmol glucuronide formed/2 mg/20 min. In an ontogenic perspective, our in vitro findings are consistent with drug metabolic studies in the human neonate in whom negligible glucuronidation but well-developed sulphate conjugation of paracetamol has been demonstrated.