Uridine 5'-(5-thio-alpha-D-glucopyranosyl pyrophosphate): chemical synthesis and activation of rat liver glycogen synthetase.

Uridine 5'-(5-thio-alpha-D-glucopyranosyl pyrophosphate), UDPTG, appears to be a potent activator of rat liver glycogen synthetase a even though it is not a substrate. At 1.0 mM, UDPTG causes over 400% activation of glycogen synthetase a activity. Activation by UDPTG is accompanied by normalization of the otherwise sigmoidal kinetics for UDPG with glycogen synthetase a and a decrease in the apparent Km for UDPG from approximately 2.0 to 0.62 mM. UDPTG inhibits catalytic activity at higher concentrations. At the concentrations examined, UDPTG has no effect on glycogen synthetase b activity. The use of glycogen synthetase free from glycogen synthetase b phosphatase and the selective inhibition of glycogen synthetase b phosphatase by 100 mM NaF-indicate that conversion of synthetase b to a is not responsible for the activation. Moreover, the use of the colorimetric assay for glycogen synthetase activity precludes effects of UDPTG on glycogen phosphorylase activity. UDPTG, chemically synthesized in 60% yield, is characterized by chromatographic and electrophoretic procedures, by its uv spectra, and by analysis of products after chemical and enzymatic hydrolysis.