Studies on the Allosteric Properties of Glycogen Synthase I

The reaction mechanism of glycogen synthase I from human polymorphonuclear leukocytes is shown to be either a rapid equilibrium random bi‐bi mechanism or an ordered sequential mechanism with uridinediphosphoglucose (UDP‐Glc) as the first substrate and UDP as the second product. The rate equations are identical at saturating glycogen concentrations. A multisite enzyme model without subunit interaction is proposed. Three sites are distinguishable on the enzyme: the catalytic site, a site for the attachment of glycogen and the allosteric binding site for glucose 6‐phosphate (glucose‐6‐P). It is proposed that the enzyme can undergo allosteric transition between two states, α and β. The α state is induced by glucose‐6‐P (activation constant 14 μM) and has a low Km for UDP‐Glc (21 μM) and a dissociation constant for the product UDP of 12 μM. For the β state the corresponding values are 5–800 μM and 4 μM. The influence of modifiers on the kinetic constants of the rate equation is on K, not V. ATP, ADP and AMP were found to favour the β state by competing with glucose‐6‐P for the allosteric site and forming a dead‐end complex. Pi, PPi, SO42−, and glycerol 2‐phosphate also competed with glu