biology : class11 cGMP Second Messenger : Receptors, Second Messengers, Gene Regulation : Hormone Action MCQ Questions and Answers
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cGMP Second Messenger
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MCQ Questions
1. A nitric oxide (NO)-releasing drug produces smooth-muscle relaxation by increasing intracellular cGMP. Which sequence most accurately describes the signaling pathway?
A.
NO activates soluble guanylyl cyclase, increasing conversion of GTP to cGMP, which activates protein kinase G
B.
NO activates adenylyl cyclase, increasing conversion of ATP to cAMP, which activates protein kinase A
C.
NO inhibits soluble guanylyl cyclase, decreasing cGMP and activating protein kinase C
D.
NO activates phosphodiesterase 5, increasing cGMP breakdown and activating myosin light-chain kinase
Correct Answer:
NO activates soluble guanylyl cyclase, increasing conversion of GTP to cGMP, which activates protein kinase G
Explanation:
NO diffuses into smooth-muscle cells and binds the heme group of soluble guanylyl cyclase. The enzyme converts GTP into cGMP, which activates protein kinase G and promotes processes that reduce smooth-muscle contraction.
2. A mutation prevents protein kinase G from binding cGMP but leaves guanylyl cyclase activity and cGMP production unchanged. What is the most likely immediate consequence?
A.
cGMP will be unable to activate its principal downstream kinase despite accumulating normally
B.
GTP will no longer be available for synthesis of cGMP
C.
NO will be unable to diffuse across the plasma membrane
D.
Phosphodiesterase 5 will convert cGMP into ATP instead of GMP
Correct Answer:
cGMP will be unable to activate its principal downstream kinase despite accumulating normally
Explanation:
Protein kinase G is a major intracellular effector of cGMP. If its cGMP-binding site is defective, cGMP synthesis can remain normal, but cGMP-dependent phosphorylation responses will be impaired.
3. A selective inhibitor of phosphodiesterase 5 is added to a cell in which soluble guanylyl cyclase is already activated by NO. Which change is most likely?
A.
A shorter cGMP signal because cGMP is converted to GMP more rapidly
B.
A prolonged cGMP signal because degradation of cGMP to GMP is reduced
C.
A complete block of GTP conversion into cGMP
D.
A replacement of cGMP by cAMP as the direct activator of protein kinase G
Correct Answer:
A prolonged cGMP signal because degradation of cGMP to GMP is reduced
Explanation:
Phosphodiesterase 5 hydrolyzes cGMP to GMP. Inhibiting this enzyme does not directly increase cGMP synthesis, but it reduces cGMP degradation and therefore prolongs and enhances signaling downstream of guanylyl cyclase.
4. Which comparison correctly distinguishes the two major guanylyl cyclase mechanisms involved in cGMP signaling?
A.
Soluble guanylyl cyclase is usually activated by NO, whereas receptor guanylyl cyclase is activated by extracellular peptide ligands such as atrial natriuretic peptide
B.
Soluble guanylyl cyclase is activated by extracellular natriuretic peptides, whereas receptor guanylyl cyclase is activated by intracellular NO
C.
Both forms are plasma-membrane receptors that convert ATP directly into cGMP
D.
Both forms synthesize cAMP, which is later converted into cGMP by protein kinase G
Correct Answer:
Soluble guanylyl cyclase is usually activated by NO, whereas receptor guanylyl cyclase is activated by extracellular peptide ligands such as atrial natriuretic peptide
Explanation:
Soluble guanylyl cyclase is a cytosolic enzyme activated primarily by NO. Receptor guanylyl cyclases are membrane-associated receptors whose extracellular ligand-binding domains can respond to natriuretic peptides and whose intracellular catalytic domains produce cGMP.
5. In retinal photoreceptor cells in darkness, which relationship between cGMP and ion channels is correct?
A.
High cGMP keeps cyclic-nucleotide-gated cation channels open, allowing a relatively continuous inward current
B.
High cGMP closes cyclic-nucleotide-gated cation channels, causing photoreceptor depolarization
C.
Low cGMP opens voltage-gated calcium channels by directly phosphorylating them
D.
cGMP is absent in darkness, so photoreceptor channels remain closed until light produces it
Correct Answer:
High cGMP keeps cyclic-nucleotide-gated cation channels open, allowing a relatively continuous inward current
Explanation:
In darkness, photoreceptors maintain relatively high cGMP concentrations. cGMP binds cyclic-nucleotide-gated cation channels and keeps them open, producing the dark current. Light activates a cascade that lowers cGMP and closes these channels.
6. A retinal mutation prevents light-activated phosphodiesterase from hydrolyzing cGMP, while guanylyl cyclase remains functional. What response to light would be expected?
A.
cGMP would remain elevated, cyclic-nucleotide-gated channels would remain open, and the normal hyperpolarization would be reduced
B.
cGMP would fall rapidly, causing persistent channel closure and an exaggerated hyperpolarization
C.
cGMP would be converted directly into cAMP, causing immediate depolarization
D.
Guanylyl cyclase would become permanently inactive because light cannot reach the retina
Correct Answer:
cGMP would remain elevated, cyclic-nucleotide-gated channels would remain open, and the normal hyperpolarization would be reduced
Explanation:
Light normally activates a phosphodiesterase that lowers cGMP in photoreceptors. If cGMP hydrolysis is blocked, cGMP-dependent cation channels remain open, preventing the normal reduction in inward current and weakening the light-induced hyperpolarization.
7. A membrane receptor containing an intracellular guanylyl cyclase domain is activated by its peptide ligand. Which molecular event occurs most directly after receptor activation?
A.
The receptor-catalytic domain converts GTP into cGMP
B.
The receptor-catalytic domain converts ATP into cAMP
C.
The receptor hydrolyzes cGMP into GMP to amplify the signal
D.
The receptor transfers phosphate from cGMP directly to DNA
Correct Answer:
The receptor-catalytic domain converts GTP into cGMP
Explanation:
Receptor guanylyl cyclases contain an intracellular catalytic domain that synthesizes cGMP from GTP after ligand binding. The newly formed cGMP can then regulate protein kinase G, ion channels, or other cGMP-sensitive targets.
8. A cell is exposed to a nonhydrolyzable cGMP analogue that binds and activates protein kinase G but cannot be degraded by phosphodiesterases. Which outcome is most likely?
A.
The cGMP-dependent response will persist longer than a response produced by normal cGMP
B.
The analogue will immediately prevent guanylyl cyclase from binding GTP
C.
Protein kinase G will be permanently converted into protein kinase A
D.
The analogue will reduce cGMP signaling by being rapidly converted into GMP
Correct Answer:
The cGMP-dependent response will persist longer than a response produced by normal cGMP
Explanation:
Normal cGMP signaling is terminated in part by phosphodiesterase-mediated hydrolysis to GMP. A nonhydrolyzable analogue that still activates protein kinase G resists this termination mechanism and therefore produces a prolonged response.
9. Which intervention would most directly reduce signaling downstream of an NO-activated cGMP pathway without preventing NO from entering the cell?
A.
Inhibit soluble guanylyl cyclase
B.
Increase the availability of GTP for guanylyl cyclase
C.
Inhibit phosphodiesterase 5
D.
Introduce a cGMP analogue that activates protein kinase G
Correct Answer:
Inhibit soluble guanylyl cyclase
Explanation:
Soluble guanylyl cyclase is the enzyme that converts the NO signal into increased cGMP. Its inhibition reduces cGMP formation and thereby decreases activation of cGMP-dependent effectors, even though NO can still enter the cell.
10. A drug activates receptor guanylyl cyclase but also strongly stimulates a cGMP-specific phosphodiesterase. What is the most likely cellular result compared with receptor activation alone?
A.
A smaller or shorter-lived increase in cGMP because synthesis is opposed by enhanced degradation
B.
A larger and more prolonged increase in cGMP because degradation is accelerated
C.
No change in cGMP because phosphodiesterases synthesize cGMP from GMP
D.
A switch from cGMP signaling to direct DNA activation by the receptor
Correct Answer:
A smaller or shorter-lived increase in cGMP because synthesis is opposed by enhanced degradation
Explanation:
Receptor guanylyl cyclase raises cGMP by converting GTP into cGMP, whereas a cGMP-specific phosphodiesterase lowers cGMP by hydrolyzing it to GMP. Simultaneous stimulation of both processes limits the magnitude and duration of the cGMP signal.
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