Components of the heme biosynthetic pathway and mixed function oxidase activity in human fetal tissues

Abstract

Components of the enzyme systems involved in heme biosynthesis and mixed function oxidase activity were examined in tissues from human fetuses between the ages of 10.8 and 17.5 weeks, aborted by hysterotomy. The activity of δ-aminolevulinic acid synthetase (ALAS) was highest in liver, and successively lower in adrenal, placenta, kidney and lung. The mean level of ALAS activity in fetal liver [61.9 ± 13.4(S.E.)nmoles ALA/g/hr] was three times higher than the level reported in human adult liver. ALAS activity was directly correlated with the concentrations of porphyrins in liver, lung and placenta ( r = 0.96). Protoporphyrin predominated in liver, while coproporphyrin predominated in lung and kidney. Ferrochelatase measured in livers from two fetuses (47.5 and 60.2 nmoles heme/g/hr) was sufficient to account for complete conversion to heme of the ALA produced by ALAS. As with other species, ALAS and ferrochelatase were found mainly in the mitochondrial subfraction of cells. Aryl hydrocarbon hydroxylation (AHH) could be measured in liver, adrenal, lung, kidney, intestine and placenta, but aminopyrine demethylation could not. In the adrenal, the concentration of cytochrome P-450 (1.92 nmoles/mg of microsomal protein) and mean AHH activity [258.2 ± 36.6 (S.E.) pmoles 3-OH benzo(a)pyrene/mg of protein/hr] were both four times higher than in the liver. In the fetal liver, the mean concentration of P-450 was within the range reported for human adult liver, but the activity of AHH [55.1 ± 17.3 (S.E.) pmoles/mg of protein/hr] was only 2 per cent of the activity reported for the adult. Cytochrome P-450 could not be detected in kidney or lung, though low levels of AHH were found (7.1 and 7.2 pmoles/mg of protein/hr). The presence of higher levels of ALAS and lower levels of cytochrome P-450 and AHH in the fetal liver than in the adrenal indicates that the activity of the heme biosynthetic pathway is not the main determinant of hemoprotein concentration and the extent of mixed function oxidase activity in human fetal tissues. The data also suggest that limitations in heme and hemoprotein synthesis may contribute to the very low mixed function oxidase activity in human fetal lung and kidney, but that other factors must account for the disparity in hepatic mixed function oxidase activity between the human fetus and adult.