Catabolism of acetylcholine MCQs With Answer

Introduction: The Catabolism of acetylcholine MCQs With Answer resource is tailored for B. Pharm students preparing for pharmacology and biochemistry assessments. This concise introduction covers acetylcholine breakdown at cholinergic synapses, the role of acetylcholinesterase and butyrylcholinesterase, mechanism of hydrolysis to choline and acetate, enzyme kinetics, clinical inhibitors (organophosphates, carbamates), diagnostic assays like Ellman’s method, and genetic/therapeutic relevance such as pseudocholinesterase deficiency and oxime reactivation. Designed to reinforce both theory and clinical application, these targeted MCQs help build strong conceptual understanding and exam readiness. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which enzyme primarily catalyzes the catabolism of acetylcholine in the synaptic cleft?

  • Choline acetyltransferase
  • Adenylate cyclase
  • Acetylcholinesterase
  • Monoamine oxidase

Correct Answer: Acetylcholinesterase

Q2. The products of acetylcholine hydrolysis by acetylcholinesterase are:

  • Acetate and choline
  • Acetyl-CoA and choline
  • Acetate and ethanol
  • Phosphate and choline

Correct Answer: Acetate and choline

Q3. Which site on acetylcholinesterase binds the quaternary ammonium of acetylcholine?

  • Catalytic triad
  • Peripheral anionic site
  • Oxyanion hole
  • Choline-binding pocket (anionic site)

Correct Answer: Choline-binding pocket (anionic site)

Q4. Which amino acids form the catalytic triad in acetylcholinesterase?

  • Serine, histidine, glutamate
  • Serine, histidine, aspartate
  • Cysteine, histidine, aspartate
  • Lysine, serine, aspartate

Correct Answer: Serine, histidine, aspartate

Q5. Which enzyme primarily synthesizes acetylcholine in cholinergic neurons?

  • Acetylcholinesterase
  • Choline acetyltransferase
  • Butyrylcholinesterase
  • Choline kinase

Correct Answer: Choline acetyltransferase

Q6. Which transporter is responsible for high-affinity uptake of choline into presynaptic terminals?

  • VAChT
  • CHT1 (Choline transporter 1)
  • DAT (Dopamine transporter)
  • NET (Norepinephrine transporter)

Correct Answer: CHT1 (Choline transporter 1)

Q7. The vesicular acetylcholine transporter (VAChT) functions to:

  • Hydrolyze acetylcholine
  • Package acetylcholine into synaptic vesicles
  • Transport choline into the cytosol
  • Produce acetyl-CoA

Correct Answer: Package acetylcholine into synaptic vesicles

Q8. Butyrylcholinesterase (BuChE) differs from acetylcholinesterase mainly by:

  • Location exclusively in synaptic cleft
  • Broader substrate specificity and plasma localization
  • Being a membrane-bound enzyme only in CNS
  • Not hydrolyzing acetylcholine at all

Correct Answer: Broader substrate specificity and plasma localization

Q9. An irreversible inhibitor of acetylcholinesterase commonly found in pesticides is:

  • Physostigmine
  • Neostigmine
  • Organophosphate (e.g., parathion)
  • Edrophonium

Correct Answer: Organophosphate (e.g., parathion)

Q10. Carbamate inhibitors of acetylcholinesterase differ from organophosphates because carbamates:

  • Cause permanent enzyme inactivation
  • Are reversible or pseudo-irreversible with spontaneous decarbamylation
  • Do not bind the active site serine
  • Enhance acetylcholinesterase activity

Correct Answer: Are reversible or pseudo-irreversible with spontaneous decarbamylation

Q11. The Ellman assay measures cholinesterase activity by detecting which product/color change?

  • Formation of indigo dye
  • Release of thiocholine reacting with DTNB to form yellow 5-thio-2-nitrobenzoate
  • Fluorescent NADH production
  • pH change due to acetate release

Correct Answer: Release of thiocholine reacting with DTNB to form yellow 5-thio-2-nitrobenzoate

Q12. In organophosphate-poisoned patients, pralidoxime (an oxime) is used to:

  • Irreversibly block acetylcholine receptors
  • Reactivate phosphorylated acetylcholinesterase if aging has not occurred
  • Act as a muscarinic antagonist
  • Hydrolyze acetylcholine directly

Correct Answer: Reactivate phosphorylated acetylcholinesterase if aging has not occurred

Q13. “Aging” of inhibited acetylcholinesterase refers to:

  • Spontaneous recovery of enzyme function
  • Dealkylation of the phosphorylated enzyme making reactivation difficult
  • Proteolytic degradation of acetylcholinesterase
  • Increased synthesis of acetylcholinesterase

Correct Answer: Dealkylation of the phosphorylated enzyme making reactivation difficult

Q14. Pseudocholinesterase deficiency clinically affects metabolism of which drug?

  • Atropine
  • Succinylcholine
  • Neostigmine
  • Pilocarpine

Correct Answer: Succinylcholine

Q15. Which kinetic parameter describes the substrate concentration at which enzyme velocity is half-maximal?

  • Vmax
  • Kcat
  • Km
  • Ki

Correct Answer: Km

Q16. Competitive inhibitors of acetylcholinesterase would be expected to:

  • Decrease Vmax without changing Km
  • Increase Vmax and decrease Km
  • Increase apparent Km without changing Vmax
  • Irreversibly inactivate the enzyme

Correct Answer: Increase apparent Km without changing Vmax

Q17. Which clinical condition is treated by acetylcholinesterase inhibitors to increase cholinergic transmission?

  • Parkinson’s disease motor symptoms
  • Myasthenia gravis
  • Essential hypertension
  • Type 2 diabetes

Correct Answer: Myasthenia gravis

Q18. In Alzheimer’s disease, cholinesterase inhibitors are used primarily to:

  • Reduce amyloid plaque formation
  • Increase synaptic acetylcholine levels to improve cognition
  • Block NMDA receptors
  • Inhibit tau phosphorylation

Correct Answer: Increase synaptic acetylcholine levels to improve cognition

Q19. Which of the following is a reversible acetylcholinesterase inhibitor used clinically?

  • Organophosphate nerve gas
  • Neostigmine
  • Physostigmine
  • Both neostigmine and physostigmine

Correct Answer: Both neostigmine and physostigmine

Q20. Which assay sample is most appropriate for measuring plasma butyrylcholinesterase activity?

  • CSF
  • Whole brain homogenate
  • Blood plasma
  • Urine

Correct Answer: Blood plasma

Q21. Acetylcholinesterase is anchored to neuronal membranes by:

  • GPI anchors and collagen-like tail subunits
  • Direct transmembrane helix only
  • Interaction with actin filaments
  • Attachment to DNA

Correct Answer: GPI anchors and collagen-like tail subunits

Q22. The rate-limiting substrate for acetylcholine synthesis in neurons is:

  • Acetyl-CoA
  • Choline uptake into the neuron
  • ATP concentration
  • Vesicle pH

Correct Answer: Choline uptake into the neuron

Q23. Which statement regarding acetylcholinesterase isoforms is correct?

  • All isoforms are identical and freely soluble
  • Isoforms differ by alternative splicing and anchoring, affecting localization
  • Only one isoform exists in humans
  • Isoforms are determined solely by post-translational phosphorylation

Correct Answer: Isoforms differ by alternative splicing and anchoring, affecting localization

Q24. Inhibition of acetylcholinesterase at a neuromuscular junction leads to:

  • Decreased acetylcholine in synaptic cleft
  • Prolonged activation of nicotinic receptors and muscle fasciculations
  • Immediate muscle paralysis due to receptor blockade
  • Degradation of nicotinic receptors

Correct Answer: Prolonged activation of nicotinic receptors and muscle fasciculations

Q25. Measurement of red blood cell acetylcholinesterase activity reflects:

  • Hepatic BuChE activity only
  • Central nervous system acetylcholinesterase exclusively
  • Systemic acetylcholinesterase levels and exposure to inhibitors
  • Renal function

Correct Answer: Systemic acetylcholinesterase levels and exposure to inhibitors

Q26. Which molecule provides the acetyl group for acetylcholine synthesis?

  • Acetate ion
  • Acetyl-CoA
  • Acetyl phosphate
  • Acetylcarnitine

Correct Answer: Acetyl-CoA

Q27. A reversible, short-acting cholinesterase inhibitor used diagnostically for myasthenia gravis is:

  • Edrophonium
  • Aspirin
  • Organophosphate
  • Atropine

Correct Answer: Edrophonium

Q28. Which organophosphate effect is mediated by overstimulation of muscarinic receptors?

  • Bronchospasm, salivation, miosis
  • Muscle paralysis only
  • Hyperglycemia
  • Peripheral neuropathy without autonomic signs

Correct Answer: Bronchospasm, salivation, miosis

Q29. The peripheral anionic site of acetylcholinesterase is important for:

  • Hydrolyzing acetate
  • Initial binding and guidance of acetylcholine into the active site
  • Binding of oximes for reactivation exclusively
  • Phosphorylation of the enzyme

Correct Answer: Initial binding and guidance of acetylcholine into the active site

Q30. Which factor can influence acetylcholinesterase catalytic efficiency in vitro?

  • pH and temperature
  • Color of the assay tube
  • Ambient light only
  • Presence of oxygen exclusively

Correct Answer: pH and temperature

Q31. Which genetic variation affects butyrylcholinesterase activity and succinylcholine metabolism?

  • CYP2D6 polymorphism
  • BCHE gene mutations
  • MAO-A promoter polymorphism
  • COMT val158met

Correct Answer: BCHE gene mutations

Q32. Which substrate is preferentially hydrolyzed by butyrylcholinesterase over acetylcholinesterase?

  • Acetylcholine exclusively
  • Succinylcholine and larger esters
  • Glycine
  • Dopamine

Correct Answer: Succinylcholine and larger esters

Q33. In the context of nerve agent exposure, which immediate therapy is useful to manage muscarinic symptoms?

  • Pralidoxime only
  • Atropine (muscarinic antagonist)
  • Physostigmine
  • Neostigmine

Correct Answer: Atropine (muscarinic antagonist)

Q34. Which laboratory technique can differentiate acetylcholinesterase from butyrylcholinesterase activity?

  • Mass spectrometry of choline
  • Substrate specificity assays using selective substrates and inhibitors
  • Hemoglobin electrophoresis
  • Urine colorimetric test

Correct Answer: Substrate specificity assays using selective substrates and inhibitors

Q35. The term “pseudo-irreversible” enzyme inhibition best describes which inhibitor class?

  • Edrophonium
  • Carbamates
  • Competitive reversible inhibitors
  • Allosteric activators

Correct Answer: Carbamates

Q36. Which statement best explains why rapid hydrolysis of acetylcholine is necessary at synapses?

  • To conserve acetylcholine energy
  • To terminate signal quickly and prevent continuous receptor activation
  • To prevent vesicle formation
  • To convert choline into acetyl-CoA

Correct Answer: To terminate signal quickly and prevent continuous receptor activation

Q37. Which method is commonly used to visualize acetylcholinesterase distribution in tissues?

  • Western blot for tyrosine hydroxylase
  • Histochemical staining for cholinesterase activity
  • PCR for choline acetyltransferase
  • CT scan

Correct Answer: Histochemical staining for cholinesterase activity

Q38. Which clinical sign indicates nicotinic receptor overstimulation due to cholinesterase inhibition?

  • Bronchorrhea
  • Miosis
  • Muscle fasciculations and weakness
  • Bradycardia exclusively

Correct Answer: Muscle fasciculations and weakness

Q39. Which of the following increases acetylcholine availability at synapses?

  • Inhibition of choline uptake
  • Blocking VAChT
  • Acetylcholinesterase inhibition
  • Depletion of acetyl-CoA

Correct Answer: Acetylcholinesterase inhibition

Q40. A high Km value for acetylcholine indicates that the enzyme:

  • Has high affinity for acetylcholine
  • Has low affinity and requires higher substrate concentration for half-maximal velocity
  • Is irreversible
  • Is activated by substrate binding

Correct Answer: Has low affinity and requires higher substrate concentration for half-maximal velocity

Q41. Which of the following is a central nervous system effect of acetylcholinesterase inhibitors used in Alzheimer’s?

  • Peripheral neuromuscular blockade
  • Improved attention and memory in some patients
  • Complete cure of disease pathology
  • Permanent increase in neuron number

Correct Answer: Improved attention and memory in some patients

Q42. The active site serine of acetylcholinesterase forms what type of intermediate during catalysis?

  • Phosphoserine with acetyl groups
  • Acyl-enzyme (acetylated serine) intermediate
  • Disulfide bridge
  • Carbamylated lysine

Correct Answer: Acyl-enzyme (acetylated serine) intermediate

Q43. Inhibition constants (Ki) are useful to quantify:

  • Substrate turnover number
  • Enzyme thermostability
  • Affinity of an inhibitor for an enzyme
  • Protein molecular weight

Correct Answer: Affinity of an inhibitor for an enzyme

Q44. Which clinical laboratory finding suggests organophosphate poisoning?

  • Elevated RBC acetylcholinesterase activity
  • Markedly reduced RBC or plasma cholinesterase activity
  • High blood glucose only
  • Elevated serum creatinine exclusively

Correct Answer: Markedly reduced RBC or plasma cholinesterase activity

Q45. Which type of receptor responds to acetylcholine at the autonomic ganglia?

  • Muscarinic M2 only
  • Nicotinic neuronal (Nn) receptors
  • Beta-adrenergic receptors
  • 5-HT3 receptors

Correct Answer: Nicotinic neuronal (Nn) receptors

Q46. Which enzyme assay substrate is commonly used to measure acetylcholinesterase in Ellman’s method?

  • Acetylthiocholine iodide
  • Acetylcholine chloride directly
  • p-Nitrophenyl phosphate
  • Glucose

Correct Answer: Acetylthiocholine iodide

Q47. BuChE activity may be clinically useful as a biomarker for:

  • Thyroid hormone levels
  • Liver synthetic function and exposure to certain toxins
  • Bone mineral density
  • Serum sodium concentration

Correct Answer: Liver synthetic function and exposure to certain toxins

Q48. Which pharmacological strategy can protect acetylcholinesterase from irreversible organophosphate binding?

  • Pre-treatment with reversible carbamate inhibitors (protective carbamylation)
  • Administration of succinylcholine
  • Giving acetylcholine intravenously
  • Blocking choline transporters

Correct Answer: Pre-treatment with reversible carbamate inhibitors (protective carbamylation)

Q49. During synaptic transmission, choline released after acetylcholine hydrolysis is mainly reused by:

  • Diffusion to glial cells for degradation
  • Uptake into the presynaptic neuron via CHT1
  • Metabolism to acetyl-CoA extracellularly
  • Excretion in urine

Correct Answer: Uptake into the presynaptic neuron via CHT1

Q50. Which structural feature of organophosphates contributes to long-lasting acetylcholinesterase inhibition?

  • Rapid hydrolysis in plasma
  • Stable P–O or P–S bond formation with active-site serine and subsequent aging
  • Lack of phosphorus atom
  • High polarity preventing tissue penetration

Correct Answer: Stable P–O or P–S bond formation with active-site serine and subsequent aging

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