A 45-year-old man with type 1 diabetes mellitus is brought to the emergency department after being found unresponsive by his wife. His capillary blood glucose is 32 mg/dL. He is administered intramuscular glucagon, which promptly restores his consciousness and raises his blood glucose levels by promoting hepatic glycogenolysis. Arrange the following steps of the intracellular signal transduction cascade in the correct chronological order, starting immediately after the medication reaches the hepatocyte.
- 1Binding of the ligand to the extracellular domain of the G protein-coupled receptor
- 2Activation of the Gs alpha subunit and its stimulation of adenylyl cyclase
- 3Conversion of intracellular ATP into cyclic AMP (cAMP)
- 4Activation of protein kinase A (PKA)
- 5Phosphorylation of target enzymes, including glycogen phosphorylase kinase
Answer
The correct sequence is: Receptor binding -> Gs subunit activation -> cAMP generation -> PKA activation -> Target enzyme phosphorylation.
The sequence correctly traces the Gs-protein coupled receptor (GPCR) pathway utilized by glucagon. The process begins with the ligand binding the receptor on the cell surface. This induces a conformational change that activates the Gs protein, causing its alpha subunit to stimulate adenylyl cyclase. Adenylyl cyclase then converts ATP into cAMP. Increased levels of intracellular cAMP subsequently activate protein kinase A (PKA). Finally, PKA phosphorylates specific target enzymes, such as activating glycogen phosphorylase kinase and inactivating glycogen synthase, thereby promoting the rapid breakdown of glycogen and the release of glucose into the blood.
Step-by-Step Solution
Key Concept
Glucagon acts via a Gs protein-coupled receptor to increase cAMP, activate PKA, and phosphorylate metabolic enzymes to rapidly induce glycogenolysis.
Estimated Time:45s