Glucagon glycogen synthesis

The same cAMP-dependent protein kinase that is responsible for phosphorylating phosphorylase kinase also catalyzes the phosphorylation of glycogen synthase. Whereas phosphorylation of glycogen phosphorylase leads to increased activity, the phosphorylation of glycogen synthase decreases its activity. As a result when glycogen breakdown is stimulated in response to glucagon, glycogen synthesis is inhibited. In this way the simultaneous operation of both enzymes associated with pseudocycle la is prevented. 

Glycogen phosphorylase isoenzymes have been isolated from liver, brain and skeletal muscle. All forms are subject to covalent control with conversion of the inactive forms (GP-b) to the active forms (GP-a) by phosphorylation on specific serine residues. This phosphorylation step, mediated by the enzyme phosphorylase kinase, is initiated by glucagon stimulation of the hepatocyte. Indeed, the same cAMP cascade which inhibits glycogen synthesis simultaneously stimulates glycogenolysis, giving us an excellent example of reciprocal control. 

Glucagon stimulation of liver cells in particular leads to phosphorylation of regulatory enzymes whereas insulin has the opposite effect. So, after a meal, we would expect glycolysis and glycogen synthesis to operate very efficiently so the control enzymes will be dephosphorylated. 

In contrast to glucagon, the peptide hormone insulin (see p. 76) increases glycogen synthesis and inhibits glycogen breakdown. Via several intermediates, it inhibits protein kinase GSK-3 (bottom right for details, see p. 388) and thereby prevents inactivation of glycogen synthase. In addition, insulin reduces the cAMP level by activating cAMP phosphodiesterase (PDE). 

The decreased insulin/glucagon ratio leads to inhibition of glycogen synthesis and increased glycogenolysis to supply some of the body s glucose needs on an immediate basis. 

Glucagon stimulates glycogen breakdown and simultaneously inhibits glycogen synthesis in the liver. 

Increased glycogen synthesis The increased insulin to glucagon ratio and the availability of glucose 6-phosphate favor glycogen synthesis, particularly if glycogen stores have been depleted as a result of exercise (see p. 124, and Figure 24.6, ). 

Feeding provokes an increase in the concentration of plasma insulin. This elevation counteracts the effects of glucagon jnenhoned earlier, Insulin also has a variety of effects independent of glucagon action and of cAMP. The most well-known glucagon-independent effect is an increase in glucose transport into muscle for the purpose of glycogen synthesis and into adipose tissue for tire purpose of fatty acid synthesis-... 

Figure 5-15. Hormonal regulation of glycogen synthesis and degradation. Solid lines indicate reactions that predominate when glucagon or epinephrine is elevated (steps 1 through 6 indicated by circled numbersy, dashed lines indicate those that predominate when insulin is elevated.

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