Question

Protein kinase B (PKB) inactivates glycogen synthase kinase (GSK3), and GSK3 inactivates glycogen synthase. Predict the effect of insulin on glycogen synthesis.

Short answer

Insulin stimulates glycogen synthesis by activating PKB, which inactivates GSK3, allowing glycogen synthase to remain active.

Step-by-step solution

Understanding the Role of PKB

Insulin activates Protein kinase B (PKB). PKB plays a significant role in multiple signaling pathways that promote glycogen synthesis by inactivating glycogen synthase kinase (GSK3).

Action of GSK3 and Implications

GSK3, when active, inhibits glycogen synthase, an enzyme responsible for glycogen synthesis. Inactivation of GSK3 allows glycogen synthase to remain active, promoting glycogen synthesis.

Linking PKB and GSK3

PKB, when activated by insulin, inactivates GSK3. This results in decreased GSK3 activity, thus removing the inhibitory effect on glycogen synthase.

Effect of Insulin on Glycogen Synthesis

With GSK3 inactivated by PKB, glycogen synthase remains active, leading to increased glycogen synthesis. Therefore, insulin ultimately stimulates glycogen synthesis by activating PKB, which in turn inactivates GSK3.

Key concepts

Protein Kinase B (PKB)

Protein Kinase B, also known as PKB or Akt, is a central player in the insulin signaling pathway. It helps mediate various cellular processes, including glycogen synthesis, growth, and survival. When insulin binds to its receptor on the cell surface, a series of events is triggered, leading to the activation of PKB.

PKB is activated through a complex cascade involving its phosphorylation. This phosphorylation is a key step that allows PKB to translocate to different areas of the cell and modulate the activity of specific substrates, one of which is glycogen synthase kinase (GSK3). By inactivating GSK3, PKB assists in promoting the synthesis of glycogen. This function is vital because glycogen acts as a primary storage form of glucose in cells, particularly in the liver and muscle tissues. Ensuring a regulated glycogen storage is crucial for maintaining blood sugar levels and providing energy during fasting or exercise periods.

Glycogen Synthesis

Glycogen synthesis is the process by which glucose molecules are linked together to form glycogen, a multi-branched polysaccharide stored in the liver and muscles. This process is primarily activated in response to increased levels of insulin, signaling that the body has sufficient energy.

The key enzyme responsible for synthesizing glycogen is glycogen synthase. It acts by facilitating the addition of glucose units from a donor molecule (UDP-glucose) to the growing glycogen chain. The activity of glycogen synthase is regulated by phosphorylation, which dictates its active or inactive state.

In a well-fed state, insulin signaling leads to the activation of PKB, which inactivates GSK3, an enzyme that normally inhibits glycogen synthase. When GSK3 is inactivated, glycogen synthase becomes active, allowing for increased glycogen synthesis. This serves as an energy reserve that the body can tap into during times of need, like fasting or intense physical activity.

Glycogen Synthase Kinase (GSK3)

Glycogen Synthase Kinase 3, abbreviated as GSK3, plays a critical role in regulating glycogen synthesis. It is a serine/threonine protein kinase known for its involvement in various cellular processes, including metabolism, cell cycle, and neuronal functions.

In the context of glycogen synthesis, GSK3 acts as a negative regulator. When GSK3 is active, it phosphorylates glycogen synthase, rendering it inactive. This phosphorylation prevents glycogen synthase from catalyzing the formation of glycogen, thus slowing down the synthesis process.

However, insulin signaling prompts the activation of PKB, which in turn phosphorylates GSK3 at specific sites, inactivating it. As a result, the inhibitory effect on glycogen synthase is lifted, allowing glycogen synthesis to proceed. Therefore, in response to insulin, the inactivation of GSK3 is a critical step in promoting glycogen storage, ensuring that energy homeostasis is maintained.