DEVELOPMENTAL CHANGES IN THE PROPERTIES OF LIVER GLUCURCNYLTRANSFERASE IN RATS

Abstract

The molecular basis for postnatal changes in glucuronyltransferase (GT) activity is not understood. The mechanisms underlying these changes were studied in fetal (F), newborn (N), and adult (A) rats using p-nitrophenol (PNP) as acceptor substrate. When assayed at 2 to 4 mM UDPGA, GT activity in F and N was greater than in A. Kinetic analysis revealed that the apparent Km for UDPGA at 0.4 mM PNP was 4 to 6 mM for F and N, and 13 to 16 mM for A. When assayed at saturating concentrations of UDPGA, GT activities in F, N and A were equivalent. Hence, the differences in activity of F, N and A at 2 to 4 mM UDPGA are due to differences in affinity of GT for UDPGA. UDP-N-acetylglucosamine (UDPNAG) is known to increase the affinity of GT for UDPGA in mature liver. UDPNAG increased GT activity 3 to 4-fold in A in the presence of 1 mM UDPGA, but had no effect in F or N. However, an activating effect of UDPNAG on GT was observed in N when the concentration of UDPGA was reduced to 0.1 mM, i.e., far below the apparent Km. These data indicate that developmental changes in synthesis of PNP-glucuranide reflect the activities of different functional forms of GT. Small amounts of the A form of GT are present at 5 days post partum, and complete development of the A form is achieved by 20 days after birth.