Inhibition of muscle phosphorylase a by 5-gluconolactone.

5-Gluconolactone is a potent inhibitor of rabbit muscle phosphorylase (I in the presence of saturating AMP. Kinetic analysis leads to the conclusion that the inhibitor binds most strongly to the enzyme-glycogen-Pi complex (KAPI = 0.025 mm), but weaker binding is also observed with the enzymeglycogen-ar-o-glucopyranose l-phosphate complex, the enzyme-glycogen complex, the enzyme-Pi complex, and the free enzyme. Dissociation constants for each of the observed inhibitor complexes have been evaluated. The kinetic data is consistent with a model in which 5-gluconolactone binds to the site in the enzyme that normally binds the glucosyl residue that is transferred between polysaccharide and Pi in the catalytic reaction. 5-Gluconolactone may be an analogue of the substrate part of the transition state of the phosphorylase reaction.