Interplay between covalent and noncovalent regulation of glycogen phosphorylase role of different effectors of phosphorylase b ec on the phosphorylase b to phosphorylase a conversion rate

Morange, M.; Buc, H.

Biochimie 61(5-6): 633-644


ISSN/ISBN: 0300-9084
Accession: 005732461

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Glycogen phosphorylase b is converted to glycogen phosphorylase a; the covalently activated form of the enzyme, by phosphorylase kinase. G-6-P, which is an allosteric inhibitor of phosphorylase b and glycogen, which is a substrate of this enzyme, are already known to have respectively an inhibiting and activating effect upon the rate of conversion from phosphorylase b to phosphorylase a by phosphorylase kinase. In the former case, this effect is due to the binding of G-6-P to glycogen phosphorylase b. In order to investigate whether or not the rate of conversion of glycogen phosphorylase b to phosphorylase a depends on the conformational state of the b substrate; the action of the most specific effectors of glycogen phosphorylase b activity was tested upon the rate of conversion from phosphorylase b to phosphorylase a at C and C: AMP and other strong activators, IMP and weak activators, G-6-P, glycogen, G-1-P and phosphate. AMP and strong activators have a very important inhibitory effect at low temperature, but not at room temperature, whereas weak activators have always a very weak, if even existing, inhibitory effect at both temperatures. The very strong inhibiting effect of G-6-P at both temperatures and the strong activating effect of glycogen were confirmed. Phosphate had a very strong inhibitory effect, whereas G-1-P had an activating effect only at room temperature and at non-physiological concentrations. The concomitant effects of substrates and nucleotides were studied. The effects of all these ligands may be direct on phosphorylase kinase, or indirect; the ligand modifying the conformation of phosphorylase b and its interaction with phosphorylase kinase. Since no control experiments with a peptidic fragment of phosphorylase b were conducted, the interpretation of these results remains putative. The differential effects observed with different nucleotides agree with the simple conformational scheme proposed earlier. Phosphorylase kinase probably recognizes differently, the different conformations of glycogen phosphorylase b. In agreement with such an explanation, the inhibiting effect of AMP is shown to be mediated by a slow isomerization, previously ascribed to a quaternary conformational change of glycogen phosphorylase b. The results (in particular, the important effect of glycogen and phosphate) are discussed in correlation with the physiological role of the different ligands as regulatory signals in the in vivo situation where phosphorylase is inserted into the glycogen particle.