Problem 12

Question

Histamine binds to the H1 G-protein-linked receptor to initiate the itchiness and airway constriction associated with an allergic response. If a mutation in the associated G-protein's alpha subunit prevented the hydrolysis of GTP how would the allergic response change? a. More severe allergic response compared to normal G-protein signaling. b. Less severe allergic response compared to normal G-protein signaling. c. No allergic response. d. No change compared to normal G-protein signaling.

Step-by-Step Solution

Verified
Answer
The correct answer is a. More severe allergic response compared to normal G-protein signaling.
1Step 1: Understand G-protein Function
A G-protein is activated when the alpha subunit binds GTP. Normally, the G-protein will hydrolyze GTP to GDP to terminate the signal.
2Step 2: Analyze the Mutation Effect
The mutation prevents the hydrolysis of GTP in the alpha subunit, meaning the G-protein will remain active longer than usual.
3Step 3: Connect to the Allergic Response
Since the G-protein remains active, it will continue to initiate signaling pathways that cause itchiness and airway constriction.
4Step 4: Determine the Outcome
Continuous active signaling likely means the response to histamine is more severe. Hence, the correct answer is 'a. More severe allergic response compared to normal G-protein signaling.'

Key Concepts

HistamineG-protein-linked receptorAllergic responseGTP hydrolysisSignal transduction
Histamine
Histamine is a small molecule that plays a crucial role in the body's immune response. It is released by immune cells known as mast cells in response to allergens. This molecule causes various symptoms associated with allergies, such as itchiness, swelling, and airway constriction. Histamine works by binding to specific receptors, one of which is the H1 G-protein-linked receptor, initiating a cascade of cellular events leading to allergic reactions.
G-protein-linked receptor
G-protein-linked receptors (GPCRs) are a large family of cell surface receptors that detect molecules outside the cell and activate internal signal transduction pathways. The H1 receptor, which binds histamine during an allergic reaction, is one such GPCR. Upon binding histamine, the receptor undergoes a conformational change, activating the associated G-protein by enabling the alpha subunit to bind GTP. This activation leads to further intracellular signaling events that propagate the allergic response symptoms.
Allergic response
An allergic response is the body's reaction to harmless substances, such as pollen or pet dander, treated as threats. Upon exposure to these allergens, immune cells release histamine and other chemicals, culminating in symptoms like itchy eyes, runny nose, and airway constriction. The process begins when histamine binds to H1 receptors on various cells, triggering a signaling cascade through G-proteins that results in these noticeable allergy signs. Without proper regulation, this response might become overly severe, causing extensive discomfort.
GTP hydrolysis
GTP hydrolysis is a crucial process in the function of G-proteins. Normally, once the GPCR activates the G-protein by allowing the alpha subunit to bind GTP, the alpha subunit will hydrolyze GTP to GDP. This hydrolysis acts as a timer, shutting off the G-protein signaling after a brief period, providing controlled regulation of the signaling pathways. If a mutation prevents GTP hydrolysis, the G-protein remains persistently active, leading to continuous signaling which, in the context of an allergic reaction, causes more severe symptoms.
Signal transduction
Signal transduction is the process by which a cell converts an external signal into a functional response. In the case of an allergic reaction, the binding of histamine to the H1 receptor is the initial signal. This signals through the G-protein, leading to a series of intracellular events. These events can include enzyme activation, ion channel modulation, and changes in gene expression. All these actions collectively manifest as the physical symptoms of an allergy, like itchiness and airway constriction. Efficient signal transduction ensures that cells respond appropriately to external stimuli, while dysregulation can lead to excessive or insufficient responses.