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 glycogen phosphorylase b from rabbit skeletal muscle has been carried out over a wide range of concentrations of AMP under the saturation of the enzyme by glycogen. The applicability of 23 different variants of the kinetic model involving the interaction of AMP and glucose 1-phosphate binding sites in the dimeric enzyme molecule is considered. A kinetic model has been proposed which assumes: (i) the independent binding of one molecule of glucose 1-phosphate in the catalytic site on the one hand, and AMP in both allosteric effector sites and both nucleoside inhibitor sites of the dimeric enzyme molecule 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 catalytic site of glycogen phosphorylase b containing two molecules of AMP occupying both allosteric effector sites; and (v) the catalytic act occurs exclusively in the complex of the enzyme with glycogen, two molecules of AMP occupying both allosteric effector sites, and two molecules of glucose 1-phosphate occupying both catalytic sites.
Klinov
S V
SV
Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky prospekt, 33, Moscow 117071, Russia. klinov@inbi.ras.ru
Kurganov
B I
BI
D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000465:Algorithms; D003198:Computer Simulation; D020536:Enzyme Activators / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D006005:Phosphorylases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012044:Regression Analysis
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D000249:Adenosine Monophosphate; D006005:Phosphorylases