Allosterism glycogen metabolism

The principal enzymes controlling glycogen metabolism—glycogen phosphorylase and glycogen synthase— are regulated by allosteric mechanisms and covalent modifications due to reversible phosphorylation and... 

Glycogen metabolism is subject to several different control mechanisms, including covalent modification and allosteric effects. 

Explain the allosteric effects of glucose on glycogen metabolism. 

The flow of intermediates through metabolic pathways is controlled by 1bir mechanisms 1) the availability of substrates 2) allosteric activation and inhibition of enzymes 3) covalent modification of enzymes and 4) induction-repression of enzyme synthesis. This scheme may at first seem unnecessarily redundant however, each mechanism operates on a different timescale (Figure 24.1), and allows the body to adapt to a wde variety of physiologic situations. In the fed state, these regulatory mechanisms ensure that available nutrients are captured as glycogen, triacylglycerol, and protein. 

Feedback can also be positive. Since AMP is a product of the hydrolysis of ATP, its accumulation is a signal to activate key enzymes in metabolic pathways that generate ATP. For example, AMP causes allosteric activation of glycogen phosphorylase, which catalyzes the first step in the catabolism of glycogen. As is shown in Fig. 11-5, the allosteric site for AMP or IMP binding is more than 3 nm away from the active site. Only a... 

Phosphorylation also can modify an enzyme s sensi-tivity to allosteric effectors. Phosphorylation of glycogen phosphorylase reduces its sensitivity to the allosteric activator adenosine monophosphate (AMP). Thus, a covalent modification triggered by an extracellular signal can override the influence of intracellular allosteric regulators. In other cases, variations in the concentrations of intracellular effectors can modify the response to the covalent modification, depending on the metabolic state of affairs in the cell. 

Enzyme activity can be regulated by covalent modification or by noncovalent (allosteric) modification. A few enzymes can undergo both forms of modification (e.g., glycogen phosphorylase and glutamine synthetase). Some covalent chemical modifications are phosphorylation and dephosphorylation, acetylation and deacetylation, adeny-lylation and deadenylylation, uridylylation and deuridyly-lation, and methylation and demethylation. In mammalian systems, phosphorylation and dephosphorylation are most commonly used as means of metabolic control. Phosphorylation is catalyzed by protein kinases and occurs at specific seryl (or threonyl) residues and occasionally at tyrosyl residues these amino acid residues are not usually part of the catalytic site of the enzyme. Dephosphorylation is accomplished by phosphoprotein phosphatases ... 

---