8.4 Regulation of glycogen metabolism

We have seen before that phosphofructokinase and the complementary enzyme fructose-1,6-bisphosphatase are regulated by both intracellular and extracellular signals. The same applies to the enzymes involved in glycogen metabolism.

The allosteric regulatory effects by ATP, AMP and glucose-6-phosphate (Figure 8.4-1a) make sense: Depletion of ATP would be an excellent reason to regenerate it by tapping into the glucose store. On the other hand, glucose-6-phosphate will be plentyful exactly when glucose itself is abundant, so it should promote glycogen synthesis rather than breakdown.

Hormonal control (Figure 8.4-1b) is similar to that of gluconeogenesis (cf. section 7.3): Protein kinase A decreases glycogen synthesis via direct phosphorylation of glycogen synthase. Glycogen breakdown is stimulated by phosphorylation of a dedicated phosphorylase kinase, which then in turn phosphorylates glycogen phosphorylase. Note that glycogen synthase and phosphorylase respond in opposite ways to phosphorylation: The first one is inactivated, the second activated.

There are regulatory differences between glycogen phosphorylase in muscle and liver: Glucose inhibits the liver enzyme but not the muscle enzyme, and Ca⁺⁺ stimulates the muscle enzyme but not the liver enzyme. Recall that Ca⁺⁺ is also the trigger for muscle contraction, so it seems that the simultaneous stimulation of glycogen breakdown occurs in anticipation of increased ATP requirement. This is an example of the usefulness of isozymes, that is enzymes that catalyze the same reaction yet are different molecules, and therefore may possess different regulatory adaptations.