Q.32 Match the molecule in column I with its function in column II

Column I

(P) Cholera toxin

(Q) Pertussis toxin

(R) IP3

(S) Caffeine

Column II

(i) modifies G𝛼i

(ii) inhibits c-AMP phosphodiesterase

(iii) modifies G𝛼𝑠

(iv) increases intracellular Ca2+ level

(A) P-iii ; Q-i; R-iv, S-ii

(B) P-iv; Q-i; R-iii, S-ii

(C) P-ii ; Q-iv; R-i, S-iii

(D) P-iii ; Q-i; R-ii, S-iv

The correct answer is (A) P-iii ; Q-i; R-iv; S-ii.
Cholera toxin modifies Gαs, pertussis toxin modifies Gαi, IP3 increases intracellular Ca²⁺, and caffeine inhibits cAMP phosphodiesterase, thereby increasing cAMP levels.​

Introduction

This signaling question tests understanding of how cholera toxin, pertussis toxin, IP3 and caffeine modulate G proteins, cAMP and intracellular Ca²⁺, which is a frequent theme in CSIR NET and other life sciences exams. Correctly matching these molecules to their targets and second‑messenger effects is essential for mastering cell signaling pathways involving Gαs, Gαi, IP3 receptors and cAMP phosphodiesterase.​

Step‑by‑step Matching of Column I and II

Column I

• (P) Cholera toxin

• (Q) Pertussis toxin

• (R) IP3

• (S) Caffeine

Column II

• (i) modifies Gαi

• (ii) inhibits c-AMP phosphodiesterase

• (iii) modifies Gαs

• (iv) increases intracellular Ca²⁺ level

1. Cholera toxin (P)

• Cholera toxin is an AB5 toxin that ADP‑ribosylates the stimulatory G protein alpha subunit Gαs, locking it in an active GTP‑bound state.​

• This persistent activation of Gαs stimulates adenylyl cyclase, causing excessive cAMP production in intestinal epithelial cells and secretory diarrhea.​

• Therefore, cholera toxin “modifies Gαs” → (iii).

So: P → (iii).

2. Pertussis toxin (Q)

• Pertussis toxin catalyzes ADP‑ribosylation of Gi family Gα proteins, inactivating them and preventing their interaction with receptors.​

• Since Gαi normally inhibits adenylyl cyclase, its inactivation leads to loss of this inhibition and increased cAMP levels.​

• Therefore, pertussis toxin “modifies Gαi” → (i).

So: Q → (i).

3. IP3 (inositol 1,4,5‑trisphosphate) (R)

• IP3 is a classical second messenger generated from PIP2 by phospholipase C activation downstream of many GPCRs and RTKs.​

• It binds to IP3 receptors on the endoplasmic reticulum, opening Ca²⁺ channels and releasing Ca²⁺ into the cytosol, thus increasing intracellular Ca²⁺ levels.​

• Therefore, IP3 “increases intracellular Ca²⁺ level” → (iv).

So: R → (iv).

4. Caffeine (S)

• Caffeine is a methylxanthine that inhibits cAMP phosphodiesterase, the enzyme that normally degrades cAMP to 5′‑AMP.​

• By blocking phosphodiesterase, caffeine prolongs and elevates intracellular cAMP levels in many cell types.​

• Therefore, caffeine “inhibits c‑AMP phosphodiesterase” → (ii).

So: S → (ii).

Putting it together:

• P → iii

• Q → i

• R → iv

• S → ii

This corresponds exactly to option (A).

Option‑by‑Option Analysis

Option (A) P-iii ; Q-i; R-iv; S-ii ✅

• P-iii: Cholera toxin modifies Gαs via ADP‑ribosylation, activating adenylyl cyclase and increasing cAMP.​

• Q-i: Pertussis toxin modifies Gαi via ADP‑ribosylation, inactivating inhibitory G proteins and indirectly raising cAMP.​

• R-iv: IP3 binds IP3 receptors on ER and releases Ca²⁺, raising cytosolic Ca²⁺.​

• S-ii: Caffeine inhibits cAMP phosphodiesterase, preventing cAMP breakdown and enhancing cAMP signaling.​

All four match known signaling mechanisms, so (A) is correct.

Option (B) P-iv; Q-i; R-iii; S-ii ❌

• P-iv: Claims cholera toxin “increases intracellular Ca²⁺ level,” which is not its defining mechanism; its primary and exam‑relevant action is Gαs modification and cAMP elevation.​

• R-iii: Assigns IP3 to “modifies Gαs,” but IP3 acts on IP3 receptors, not on G proteins, and specifically controls Ca²⁺ release.​

Because P and R are wrongly matched, option (B) is incorrect.

Option (C) P-ii ; Q-iv; R-i; S-iii ❌

• P-ii: Says cholera toxin inhibits cAMP phosphodiesterase, but its major target is Gαs, not phosphodiesterase; it activates adenylyl cyclase instead.​

• Q-iv: Pertussis toxin does not directly increase intracellular Ca²⁺; it modifies Gαi.​

• R-i: IP3 does not modify Gαi; it acts on ER Ca²⁺ channels.​

• S-iii: Caffeine does not modify Gαs; it inhibits phosphodiesterase.​

All four pairings are mismatched, so option (C) is entirely wrong.

Option (D) P-iii ; Q-i; R-ii; S-iv ❌

• P-iii: Correct for cholera toxin (modifies Gαs).​

• Q-i: Correct for pertussis toxin (modifies Gαi).​

• R-ii: Incorrect, because IP3 does not inhibit cAMP phosphodiesterase; it releases Ca²⁺ from ER.​

• S-iv: Incorrect, since caffeine primarily acts on phosphodiesterase (and ryanodine receptors) rather than serving as a classical “increase intracellular Ca²⁺” messenger like IP3.​

Because R and S are swapped, option (D) is incorrect.

Quick Concept Table

This mechanistic mapping is exactly what the exam question tests, giving option (A) as the correct choice.