Stimulatory Adenylate Cyclase GPCR Signaling: Videos & Practice Problems

The stimulatory adenylate cyclase GPCR signaling pathway initiates with epinephrine binding to the beta adrenergic GPCR, causing a conformational shift that activates the G protein. This leads to GDP being replaced by GTP, allowing the alpha subunit to dissociate and activate the effector enzyme adenylate cyclase. Adenylate cyclase then converts ATP into cyclic AMP (cAMP), a secondary messenger that activates protein kinase A (PKA), resulting in cellular responses like increased energy mobilization. The pathway concludes with the hydrolysis of GTP to GDP, resetting the system for future signaling.

Stimulatory Adenylate Cyclase GPCR Signaling

The adenylate cyclase GPCR signaling pathway is a crucial mechanism in cellular communication, particularly in response to stress or emergencies, often referred to as the fight or flight response. This pathway is initiated when the hormone epinephrine, also known as adrenaline, binds to a specific type of G Protein Coupled Receptor (GPCR), namely the beta adrenergic GPCR. This binding triggers a series of events that can be broken down into six key steps, forming a cycle that begins and ends at the same point.

In the first step, the binding of epinephrine to the beta adrenergic GPCR induces a conformational change in the receptor. This change is essential as it activates a stimulatory G protein, known as G_s, in the second step. The activation involves the exchange of GDP (guanosine diphosphate) for GTP (guanosine triphosphate) on the alpha subunit of the G protein, transitioning it from an inactive to an active state.

Step three sees the activated alpha subunit dissociating from the beta and gamma subunits of the G protein and moving towards the effector enzyme, adenylate cyclase. In step four, the alpha subunit binds to adenylate cyclase, activating it. This activation is pivotal as it allows adenylate cyclase to convert ATP (adenosine triphosphate) into cAMP (cyclic AMP), a secondary messenger, in step five. The production of cAMP is critical as it activates protein kinase A (PKA), which then initiates various cellular responses, including the breakdown of glycogen and fat to provide energy for the fight or flight response.

Finally, in step six, the signaling pathway is terminated. The alpha subunit hydrolyzes GTP back to GDP, returning to its inactive form and reassembling with the beta and gamma subunits. This process resets the GPCR, allowing the pathway to start anew. Understanding this cycle is essential for grasping how cells respond to external stimuli and manage energy resources during critical situations.

Stimulatory Adenylate Cyclase GPCR Signaling

Stimulatory adenylate cyclase signaling through G protein-coupled receptors (GPCRs) is a complex process that involves several key components and events. The pathway begins when an extracellular ligand, such as epinephrine (adrenaline), binds to the beta adrenergic GPCR. This binding induces a conformational change in the GPCR, which facilitates the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on the G protein, activating it.

The activated G protein consists of three subunits: alpha, beta, and gamma. Upon activation, the alpha subunit dissociates from the beta and gamma subunits and moves towards the effector enzyme, adenylate cyclase. The role of adenylate cyclase is to convert adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP), a secondary messenger that plays a crucial role in cellular signaling.

Once cAMP is produced, it activates protein kinase A (PKA), which then initiates a series of cellular responses. This signaling pathway can be remembered through a creative narrative that likens the process to a camping trip. In this analogy, the ligand binding to the GPCR is represented by packing luggage, while the conformational change in the GPCR is akin to preparing for the trip. The exchange of GDP for GTP is symbolized by swapping an empty gas can for a full one, indicating the activation of the G protein.

As the story progresses, the alpha subunit, depicted as a hero, goes to rent a car (adenylate cyclase) and fills it with gas (activates adenylate cyclase). The car then drives to the campsite, representing the production of cAMP. Finally, parking the car symbolizes the activation of PKA, leading to the ultimate cell response, illustrated by cooking s'mores.

This narrative not only aids in memorizing the sequence of events but also emphasizes the importance of each component in the signaling pathway. Understanding this process is crucial for grasping how cells respond to external signals and regulate various physiological functions.

Which of the following represents the best order of signal transduction for the β-adrenergic receptor?

• A. Hormone → receptor tyrosine kinase → G-protein → protein kinase A → cAMP → cellular effects.
• B. Ligand → receptor → secondary messenger → G-protein → protein kinase A → cellular effects.
• C. Hormone → G-protein → receptor → cAMP → protein kinase A → cellular effects.
• D. Hormone → receptor → G-protein → second messenger → protein kinase A → cellular effects.

Answer: (D)

Which of the following molecules is NOT involved in signal transduction of the β-adrenergic GPCR?

• A. GTP.
• B. ATP.
• C. cAMP.
• D. cGMP.
• E. GDP.

Answer: (D)

Which of the following reactions does the enzyme adenylate cyclase catalyze?

• A. cATP to cAMP.
• B. GTP to cGMP.
• C. ATP to cADP.
• D. cGMP to GTP.
• E. ATP to cAMP.

Answer: (E)

In response to a ligand binding a GPCR, a particular G protein (G _s) activates adenylate cyclase. If a cell has a mutation where the G protein can no longer hydrolyze GTP, which of the following would be the result?

• A. Cellular levels of cAMP would go down in response to ligand binding.
• B. Cellular levels of cAMP would go up independent of ligand binding.
• C. The ligand would not be able to bind to the receptor.
• D. Cellular levels of cAMP would not change.
• E. Adenylate Cyclase would always remain inactive.

Answer: (B)

When epinephrine binds to its GPCR activating the cAMP cascade, all of the following happen EXCEPT:

• A. GDP dissociates from the G protein as GTP associates.
• B. The alpha-subunit of the G protein activates adenylate cyclase and cAMP is produced.
• C. G protein is activated and diffuses away from the cell membrane into the nucleus.
• D. The alpha-subunit of the G protein hydrolyzes GTP and becomes inactive.
• E. The alpha-subunit of the G protein bound to GDP reassociates with the beta & gamma-subunits.

Answer: (C)

Here’s what students ask on this topic:

What is the role of epinephrine in the stimulatory adenylate cyclase GPCR signaling pathway?

Epinephrine, also known as adrenaline, is the extracellular ligand that initiates the stimulatory adenylate cyclase GPCR signaling pathway. When epinephrine binds to the beta adrenergic GPCR on the cell surface, it causes a conformational shift in the receptor. This shift activates the associated G protein by promoting the exchange of GDP for GTP on the alpha subunit. The activated alpha subunit then dissociates and activates adenylate cyclase, leading to the production of cyclic AMP (cAMP) and subsequent activation of protein kinase A (PKA), which triggers various cellular responses, such as increased energy mobilization for the fight-or-flight response.

How does the G protein become activated in the stimulatory adenylate cyclase GPCR signaling pathway?

The G protein becomes activated in the stimulatory adenylate cyclase GPCR signaling pathway through a series of steps initiated by the binding of epinephrine to the beta adrenergic GPCR. This binding causes a conformational shift in the GPCR, which in turn activates the G protein. Specifically, the alpha subunit of the G protein exchanges GDP (the low-energy form) for GTP (the high-energy form). This exchange activates the alpha subunit, allowing it to dissociate from the beta and gamma subunits and interact with the effector enzyme adenylate cyclase, leading to further downstream signaling events.

What is the function of adenylate cyclase in the GPCR signaling pathway?

Adenylate cyclase is the effector enzyme in the stimulatory adenylate cyclase GPCR signaling pathway. Once activated by the GTP-bound alpha subunit of the G protein, adenylate cyclase catalyzes the conversion of ATP into cyclic AMP (cAMP). cAMP acts as a secondary messenger that activates protein kinase A (PKA). PKA then phosphorylates various target proteins, leading to cellular responses such as increased glycogen and fat breakdown, which provide the energy needed for the fight-or-flight response. Thus, adenylate cyclase plays a crucial role in amplifying the signal initiated by epinephrine binding to the GPCR.

What is the significance of cyclic AMP (cAMP) in the stimulatory adenylate cyclase GPCR signaling pathway?

Cyclic AMP (cAMP) is a critical secondary messenger in the stimulatory adenylate cyclase GPCR signaling pathway. Once adenylate cyclase is activated by the GTP-bound alpha subunit of the G protein, it converts ATP into cAMP. cAMP then activates protein kinase A (PKA), which phosphorylates various target proteins to elicit specific cellular responses. These responses include the breakdown of glycogen and fat, providing the energy necessary for the fight-or-flight response. Therefore, cAMP serves as a key intermediary that transduces the extracellular signal (epinephrine binding) into a wide range of intracellular actions.

How is the stimulatory adenylate cyclase GPCR signaling pathway terminated?

The stimulatory adenylate cyclase GPCR signaling pathway is terminated through the hydrolysis of GTP to GDP on the alpha subunit of the G protein. This hydrolysis reaction is catalyzed by the intrinsic GTPase activity of the alpha subunit. Once GTP is hydrolyzed to GDP, the alpha subunit becomes inactive and reassociates with the beta and gamma subunits, forming the inactive heterotrimeric G protein. Additionally, the ligand (epinephrine) dissociates from the beta adrenergic GPCR, resetting the receptor to its inactive state. This termination process ensures that the signaling pathway is tightly regulated and can be reactivated when needed.