Studies of the perinatal differences in the activity of hepatic δ-aminolevulinic acid synthetase

Abstract

Hepatic δ-aminolevulinic acid (ALA) synthetase activity in prenatal rats, rabbits and guinea pigs is four to eight times the adult level. During the period of elevated activity, ALA synthetase is relatively much less responsive to induction by 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) or to repression by hemin than is observed in adult rats and rabbits. No induction of ALA synthetase could be demonstrated in fetal rats. In newborn rabbits, hemin caused no significant reduction in ALA synthetase activity, whereas the adult enzyme activity was reduced to 32 per cent of control. This difference in response to hemin was also demonstrated in fetal and newborn rats. Refractoriness to induction decreases as enzyme activity decreases to adult levels. These studies indicate that the neonate may not regulate the activity of hepatic ALA synthetase at the same level as the adult. It is suggested that increasing repression of the enzyme to lower basal levels occurs as the animals mature, bringing the activity and response to DDC and hemin to the levels observed in adults. Perinatal alterations in the regulation of hepatic ALA synthetase activity may account for some of the problems associated with heme metabolism in the newborn and the toxic effects of bilirubin and various drugs.