Combined kinetic mechanism describing activation and inhibition of muscle glycogen phosphorylase b by adenosine 5 '-monophosphate

The kinetic analysis of the glycogen chain growth reaction catalyzed by gly cogen phosphorylase b from rabbit skeletal muscle has been carried out over a wide range of concentrations of AMP under the saturation of the enzyme b y glycogen. The applicability of 23 different variants of the kinetic model involving the interaction of ANT and glucose 1-phosphate binding sites in the dimeric enzyme molecule is considered. A kinetic model has been propose d which assumes: (i) the independent binding of one molecule of glucose 1-p hosphate in the catalytic site on the one hand, and AMP in both allosteric effector sites and both nucleoside inhibitor sites of the dimeric enzyme mo lecule bound by glycogen on the other hand; (ii) the binding of AMP in one of the allosteric effector sites results in an increase in the affinity of other allosteric effector site to AMP; (iii) the independent binding of AMP to the nucleoside inhibitor sites of the dimeric enzyme molecule; (iv) the exclusive binding of the second molecule of glucose 1-phosphate in the cat alytic site of glycogen phosphorylase b containing two molecules of AMP occ upying both allosteric effector sites; and (v) the catalytic act occurs exc lusively in the complex of the enzyme with glycogen, two molecules of AMP o ccupying both allosteric effector sites, and two molecules of glucose I-pho sphate occupying both catalytic sites. (C) 2001 Elsevier Science B.V. All r ights reserved.