Perinatal developmental changes in hepatic UDP-glucuronyltransferase.
Postnatal developmental changes in hapatic microsomal UDP-glucuronyltransferase were studied in the rat. The previously reported postnatal decline in the capacity of microsomal fractions to glucuronidate p-nitrophenol was found to be observable in unperturbed preparations only at non-saturating concentrations of the substrate UDP-glucuronic acid. At saturating concentrations of UDP-glucuronic acid, activity is identical in newborns and adults. Kinetic analysis revealed that the enzyme from liver of newborns has a much higher affinity for UDP-glucuronic acid than does the enzyme in adults, but the same activity at Vmax. On the other hand, the enzyme from adult liver microsomal fractions can be activated by the physiological allosteric effector UDP-N-acetylglucosamine, whereas the enzyme from newborns is largely unaffected by it. Thus it appears that the number of enzyme active sites is not changing; rather, the enzyme is maturing to a more highly regulable form. There were also differences between the enzymes in newborns and adults in their response to perturbation of the membrane-lipid environment by detergent and phospholipase A. Possible interpretations of these differences are discussed.
D000375:Aging; D000818:Animals; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006168:Guinea Pigs; D007700:Kinetics; D008099:Liver / Q000196:embryology / Q000254:growth & development; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009596:Nitrophenols / Q000378:metabolism; D010741:Phospholipases A / Q000494:pharmacology; D051381:Rats; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
D009596:Nitrophenols; D014535:Uridine Diphosphate Glucuronic Acid; D014537:Uridine Diphosphate N-Acetylglucosamine; D014453:Glucuronosyltransferase; D010741:Phospholipases A