Question

Glycogen is a complex polymer of glucose molecules involved in the storage of energy in many organisms. Depending on the signals received by a cell, different enzymes are activated, which will lead to either the synthesis or breakdown of glycogen. The product of glycogen breakdown, glucose 1-phosphate, can be modified into glucose 6-phosphate, an intermediate of glycolysis (Figure 1).

Figure 1. Glycogen synthesis and breakdown
In the liver, glycogen synthase and glycogen phosphorylase are regulated by kinases. These kinases transfer phosphate groups from ATP to amino acids in glycogen synthase and glycogen phosphorylase. Phosphorylase kinase B (PKB) is a kinase that regulates glycogen synthase kinase 3 (GSK3) activity. GSK3 regulates the activity of glycogen synthase. Phosphorylase kinase (PK) regulates the activity of glycogen phosphorylase. The activity of these kinases depends on the activation of signaling pathways in response to the binding of specific cell signals, including insulin and glucagon, to their receptors (Figure 2).

Figure 2. A simplified model of signaling pathways in a liver cell that are activated by insulin and glucagon
A cell where PKB is always active has a mutation that results in the permanent activation of GSK3. Based on the information in Figure 2, predict the effect of this mutation on the activity of glycogen synthase. Justify your prediction.

Describe the process that results in the activation of multiple copies of PKB in response to the binding of a single molecule of insulin to its receptor. Explain why insulin can stimulate the activation PKB of but not the activation of PK.
Explain why an increase in glycogen phosphorylase activity might result in an increase in
O2 consumption in the cell.

A certain type of tumor results in the overproduction of glucagon. Researchers claim that treatment with insulin can counteract the effects of the excess glucagon on the pathway shown in Figure 2. Provide reasoning to justify the researchers' claim.

Answer 1

The effect of the mutation resulting in the permanent activation of GSK3 on the activity of glycogen synthase would likely be inhibition.

• GSK3 is known to regulate the activity of glycogen synthase and its activation would likely lead to decreased activity of glycogen synthase, meaning less glycogen synthesis and more breakdown.
• Insulin binding to its receptor results in the activation of multiple copies
• The process that results in the activation of multiple copies of PKB in response to the binding of a single molecule of insulin to its receptor is known as insulin signaling cascade.
• Insulin binding to its receptor leads to the activation of intracellular signaling pathways, such as the PI3K/Akt pathway, which results in the activation and phosphorylation of PKB.
• This phosphorylated form of PKB can then activate multiple copies of itself leading to a downstream cascade of events.
• Insulin can stimulate the activation of PKB but not the activation of PK because the two kinases are regulated by different signaling pathways. PKB is activated through the PI3K/Akt pathway while PK is activated through the cAMP-dependent pathway.
• Insulin activates the PI3K/Akt pathway but not the cAMP-dependent pathway, leading to the activation of PKB but not PK.
• An increase in glycogen phosphorylase activity might result in an increase in O2 consumption in the cell because glycogen phosphorylase catalyzes the breakdown of glycogen to glucose 1-phosphate, which is then converted to glucose 6-phosphate, an intermediate of glycolysis.
• The conversion of glucose 1-phosphate to glucose 6-phosphate requires energy in the form of ATP, which is generated through the oxidation of glucose in the cell. This process requires oxygen, leading to an increase in O2 consumption.
• The researchers' claim that treatment with insulin can counteract the effects of the excess glucagon on the pathway shown in Figure 2 is likely based on the fact that insulin and glucagon have opposing effects on the regulation of glycogen metabolism. Insulin promotes glycogen synthesis and storage while glucagon promotes glycogen breakdown and glucose release.
• In the presence of an overproduction of glucagon, treatment with insulin could help to counteract the effects of glucagon by promoting glycogen synthesis and storage and decreasing glycogen breakdown and glucose release.

#SPJ1