Human Physiology - cAMP Second Messenger

Summary

In this lecture, Dr. Ketchum explains the cyclic AMP second messenger system, focusing on its key components like G-protein linked receptors, adenylate cyclase, and protein kinase A. The process begins with a lipophobic ligand binding to a receptor, activating the G-protein, which in turn stimulates adenylate cyclase to convert ATP into cyclic AMP. This activates protein kinase A, which phosphorylates proteins, resulting in a cellular response. The lecture also covers how the system is turned off, involving the degradation of ligands, GTP hydrolysis, and enzymes like phosphodiesterase and phosphatase.

Takeaways

• 🔬 The lecture focuses on membrane-bound, mediated responses, specifically G-protein linked receptors.
• 🧪 The cyclic AMP second messenger system is emphasized in this discussion.
• 📊 Key players in the cyclic AMP pathway include the receptor, G protein, adenylate cyclase, cyclic AMP, and protein kinase A.
• ⚛️ The ligand, which must be lipophobic, binds to the receptor to initiate the response.
• 🚶‍♂️ The activated G protein causes GDP to fall off the alpha subunit, replaced by GTP, which leads to activation of adenylate cyclase.
• ⚡ Adenylate cyclase converts ATP into cyclic AMP, which then activates protein kinase A.
• 🧬 Protein kinase A phosphorylates a protein, leading to a specific cellular response.
• 🛑 The system must be turned off after the response to prevent it from being continuous.
• ⏳ To deactivate, the ligand detaches, the G protein deactivates by hydrolyzing GTP, and cyclic AMP is broken down by phosphodiesterase.
• 🧹 Phosphatase dephosphorylates the protein, stopping the response within the cell.

Q & A

What is the main focus of the lecture?

The main focus of the lecture is on membrane-bound, mediated responses, specifically focusing on G-protein-linked receptors and the cyclic AMP second messenger system.

What role does cyclic AMP play in this system?

Cyclic AMP acts as a second messenger in the G-protein-linked receptor system, which activates protein kinase A and triggers phosphorylation of proteins, leading to a cellular response.

What are the key components involved in the cyclic AMP second messenger system?

The key components include the receptor, G protein, adenylate cyclase (the amplifier enzyme), cyclic AMP (the second messenger), and protein kinase A.

How is the G protein activated?

The G protein is activated when the ligand binds to the receptor, causing GDP to fall off the alpha subunit. GTP then binds to the alpha subunit, which slides over to activate adenylate cyclase.

What happens when adenylate cyclase is activated?

When adenylate cyclase is activated, it converts ATP into cyclic AMP, which then activates protein kinase A, leading to phosphorylation of proteins inside the cell.

How is the cyclic AMP system turned off?

The system is turned off when the ligand dissociates from the receptor, the G protein is deactivated through hydrolysis of GTP to GDP, cyclic AMP is broken down by phosphodiesterase, and phosphatase dephosphorylates proteins.

What is the role of phosphodiesterase in this system?

Phosphodiesterase breaks down cyclic AMP, lowering its levels in the intracellular fluid, which helps in deactivating the cyclic AMP system.

Why is it important to deactivate the cyclic AMP system?

It is important to deactivate the cyclic AMP system to prevent prolonged cellular responses. For example, if heart rate is elevated due to a sympathetic response, it should return to normal after the stimulus is gone.

What is the function of phosphatase in the cyclic AMP system?

Phosphatase dephosphorylates proteins that were phosphorylated by protein kinase A, helping to turn off the cellular response initiated by the cyclic AMP system.

What type of ligand is required to activate the cyclic AMP system?

The ligand must be lipophobic in order to bind to the receptor and activate the cyclic AMP second messenger system.