Which modification increases acetylcholine's stability to gastric acid and esterases?

Which modification increases acetylcholine's stability to gastric acid and esterases?

• A. Using steric shielding for the ester group and turning the acetyl group into a urethane
• B. Removing any steric shielding
• C. Adding a bulky hydrophobic substituent to the aromatic ring
• D. Increasing the rate of enzymatic hydrolysis

Answer: (A)

The idea being tested is how to make acetylcholine more resistant to stomach acid and to the enzymes that chew up esters. The most effective approach is to shield the ester group so enzymes can’t easily reach it, and to replace the labile acetyl ester with a more stable carbamate (urethane) linkage. Steric shielding around the ester slows or blocks esterases and reduces acid-catalyzed hydrolysis, while converting the acetyl group into a urethane creates a carbamate bond that is far less susceptible to enzymatic breakdown than a simple acetate ester. Together, these changes markedly increase stability in gastric conditions and against esterases, giving longer-lasting activity. Removing shielding would leave the molecule exposed to rapid hydrolysis, adding a bulky substituent on the aromatic ring doesn’t directly prevent ester hydrolysis, and increasing enzymatic hydrolysis would decrease stability.

The idea being tested is how to make acetylcholine more resistant to stomach acid and to the enzymes that chew up esters. The most effective approach is to shield the ester group so enzymes can’t easily reach it, and to replace the labile acetyl ester with a more stable carbamate (urethane) linkage. Steric shielding around the ester slows or blocks esterases and reduces acid-catalyzed hydrolysis, while converting the acetyl group into a urethane creates a carbamate bond that is far less susceptible to enzymatic breakdown than a simple acetate ester. Together, these changes markedly increase stability in gastric conditions and against esterases, giving longer-lasting activity. Removing shielding would leave the molecule exposed to rapid hydrolysis, adding a bulky substituent on the aromatic ring doesn’t directly prevent ester hydrolysis, and increasing enzymatic hydrolysis would decrease stability.