Effect of some nucleotides on the regulation of glycosaminoglycan biosynthesis

The effect of some nucleotides on UDP-glucose dehydrogenase (EC, 1.1.1.22) and UDP-glucose 4'-epimerase (EC, 5.1.3.2) extracted from epiphysial-plate cartilage of newborn pigs was investigated. UDP-xylose acts as a co-operative allosteric inhibitor of UDP-glucose dehydrogenase, whereas it does not inhibit UDP-glucose 4'-epimerase activity: the inhibition of UDP-glucose dehydrogenase results in an increase of UDP-galactose synthesis, in agreement with the equilibrium constant of UDP-glucose 4'-epimerase reaction. Because of the presence of UDP-glucose 4'-epimerase activity in the nezyme extract, the addition of UDP-galactose induces an increase in reaction rate of UDP-glucose dehydrogenease. NADH inhibits both UDP-glucose dehydrogenase and UDP-glucose 4'-epimerase activities; in the presence of non-saturating NAD concentrations, NADH acts as a co-operative allosteric inhibitor of both enzymes. The Inhibitory effect of NADH seems to be strickingly correlated with the value of NAD/NADH ratio and pH. In any case, the percentage inhibition of UDP-glucose 4'-epimerase, under the same experimental conditions, is always higher than that of UDP-glucose dehydrogenase.