REGULATION OF MUSCLE GLYCOGEN SYNTHETASE BY METABOLITES . DIFFERENTIAL EFFECTS ON I AND D FORMS

Both the glucose 6-phosphate independent (I) and the glucose 6-phosphate dependent (D) forms of rat muscle glycogen synthetase are inhibited by adenosine triphosphate (ATP), adenosine diphosphate (ADP), and Pi. The inhibition is, kinetically, of the competitive type with respect to uridine diphosphate glucose (UDP-glucose). Glucose 6-phosphate reverses this inhibition, without affecting, at pH 6.6, the Km for UDP-glucose. UDP, one of the reaction products, is a strong inhibitor and its effect is not reversed by glucose 6-phosphate. Photooxidation of the I form in the presence of methylene blue causes a preferential loss of the inhibition by ATP, as compared to that by UDP. The sum of this evidence suggests that UDP-glucose and ATP bind to different sites. At low concentrations of glucose 6-phosphate, within the physiological range, the D form is much more strongly inhibited by ATP than the I form. Therefore, under most conditions, probably only the latter is significantly active. These results provide a physiological meaning for the interconversion of the two enzymatic forms. The metabolic control of the biosynthesis of reserve material is discussed in the light of these findings. © 1968, American Chemical Society. All rights reserved.