Liver glycogen synthase in the developing foetal rat.

Kinetic constants for liver glycogen synthase (UDPglucose: glycogen 4-alpha-D-glucosyltransferase, EC 2.4.1.11) with respect to UDPglucose have been measured in foetal liver homogenates from samples taken during late gestation (days 17-22) and the first hours after birth. The V of the inactive form of glycogen synthase increased markedly in this period and there was a significant increase in V of the active enzyme to a maximum at day 20 of gestation. The Km for UDPglucose measured in the presence of glucose-6-P (total activity) did not vary greatly, mean values of 0.51 +/- 0.04 mM. Values derived for the inactive enzyme were almost identical. In contrast, Km values for active glycogen synthase in foetal livers during gestation were significantly higher than those for adult liver. Highest values were seen at day 19 of gestation (1.84 +/- 0.08 mM) followed by a steady fall to 0.55 +/- 0.05 mM in the newborn compared with a mean value of 0.48 +/- 0.04 mM for adult liver. Existence of a reduced affinity of active glycogen synthase for UDPglucose must be recognized when assaying the enzyme in foetal liver, particularly when extrapolating values to rates of glycogen synthesis in vivo. Data were obtained only after removal of an amylase-like contaminant from foetal liver samples which invalidated the radioassay of glycogen synthase. This work illustrates the care needed in the analysis of foetal tissue and the interpretation of resulting data when utilizing methods developed for adult tissue.