Postnatal development of mixed-function oxidation and conjugation in hemoglobin-free perfused rat liver

In perfused livers from normal developing rats, rates of p-nitroanisole O-demethylation, nearly undetectable at 8 days of age, increased progressively to a maximum of 5.1 mumol of p-nitrophenol formed per gram of liver wet weight per hour by 20 days of age. However, by 30 days of age, the rate of p-nitrophenol formation decreased to 2.8 mumol/g/h, in spite of a 300% increase in microsomal p-nitroanisole O-demethylase activity between 20 and 30 days of age. Conjugation of p-nitrophenol in perfused livers was minimal before 16 days of age. Subsequently, rates of conjugation of p-nitrophenol increase in parallel with the development of hepatic glycogen metabolism and uridine diphosphate-glucuronyltransferase activity. At all stages of development studied (8-30 days), phenobarbital treatment increased the liver weight, cytochrome P-450 content and and in vitro p-nitroanisole O-demethylase and glucuronyltransferase activities. In perfused livers from phenobarbital-treated pups, mixed-function oxidation and conjugation increased in parallel with the development of the microsomal enzymes. These data indicate that both the development of microsomal enzyme activity and the availability of required cofactors (e.g. NADPH) influence rates of mixed-function oxidation and conjugation in intact liver during development.