Effect of development on the activity of microsomal drug-metabolizing enzymes in rat liver.
1. The activity of rat liver microsomal drug-metabolizing enzymes was determined at various ages between 6 and 100 days post natum. The enzymes studied were: aromatic hydroxylases by using as substrate biphenyl, which is metabolized by oxidation to 2- and 4-hydroxybiphenyl; nitroreductase by using p-nitrobenzoate as substrate, which is metabolized by reduction to p-aminobenzoate; glucuronyl synthetase by using 4-methylumbelliferone as the substrate, which is conjugated to give 4-methylumbelliferone glucuronide, and cytochrome P-450, which is regarded as the major terminal mixed-function oxidase in hepatic microsomal hydroxylations. 2. The activity of biphenyl 2-hydroxylase reached a peak at 21 days, biphenyl 4-hydroxylase and 4-methyl glucuronyl transferase at 24 days, cytochrome P-450 at 31 days, and p-nitrobenzoate reductase at 38 days of age. After the peak activity had been reached, the activity of each enzyme decreased with age, and in the case of biphenyl 2-hydroxylase the activity fell to a negligible value at 52 days of age. 3. Neither the addition of Triton X-100 to the incubation medium nor the treatment of the animals with phenobarbital resulted in any increase in the activity of biphenyl 2-hydroxylase at 52 days of age. 4. The activity of biphenyl 2-hydroxylase was threefold higher in rats fed on a synthetic diet than in rats fed on a commercial stock diet. 5. These findings are discussed.
D000367:Age Factors; D000818:Animals; D001565:Benzoates / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism; D002498:Centrifugation; D003580:Cytochromes / Q000032:analysis; D004032:Diet; D005260:Female; D005965:Glucuronates / Q000096:biosynthesis; D008099:Liver / Q000254:growth & development* / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000032:analysis / Q000201:enzymology* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009929:Organ Size; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology
D001565:Benzoates; D001713:Biphenyl Compounds; D003580:Cytochromes; D005965:Glucuronates; D013501:Surface-Active Agents; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C021870:4-nitrobenzoate reductase; D010634:Phenobarbital