Phase I metabolism MCQs With Answer

Phase I metabolism MCQs With Answer

Phase I metabolism is a key topic for B. Pharm students, covering enzymatic reactions that modify drugs via oxidation, reduction and hydrolysis. This introduction focuses on cytochrome P450s, flavin monooxygenases, esterases, and key concepts such as regioselectivity, stereoselectivity, bioactivation, enzyme kinetics, inhibitors and polymorphisms. These Phase I metabolism MCQs With Answer help reinforce mechanisms, clinical implications, experimental models and drug–drug interactions important for pharmacokinetics and drug safety. Clear explanations and targeted practice improve exam readiness and practical understanding of metabolic pathways. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which enzyme family is primarily responsible for oxidative Phase I drug metabolism in the liver?

• Uridine diphosphate glucuronosyltransferases
• Cytochrome P450 monooxygenases
• Glutathione S-transferases
• N-acetyltransferases

Correct Answer: Cytochrome P450 monooxygenases

Q2. Which cofactor is essential for cytochrome P450 catalytic activity?

• ATP
• NADPH
• CoA
• UDP-glucuronic acid

Correct Answer: NADPH

Q3. Which Phase I reaction converts an ester into an alcohol and a carboxylic acid?

• N-dealkylation
• Hydrolysis
• Oxidative deamination
• Sulfoxidation

Correct Answer: Hydrolysis

Q4. Which CYP isoform is most often implicated in drug–drug interactions due to its high abundance and broad substrate specificity?

• CYP2D6
• CYP3A4
• CYP1A2
• CYP2E1

Correct Answer: CYP3A4

Q5. A drug showing first-pass metabolism primarily undergoes which process?

• Renal elimination before systemic circulation
• Metabolism in the gut wall and liver during absorption
• Direct conjugation in plasma
• Excretion via bile without modification

Correct Answer: Metabolism in the gut wall and liver during absorption

Q6. Which Phase I reaction introduces an oxygen atom into a substrate, often forming a hydroxyl group?

• Dehydrogenation
• Hydroxylation
• Nitration
• Acetylation

Correct Answer: Hydroxylation

Q7. Which term describes an enzyme that is permanently inactivated by forming a covalent bond with the enzyme during metabolism?

• Competitive inhibitor
• Mechanism-based (suicide) inhibitor
• Noncompetitive inhibitor
• Allosteric activator

Correct Answer: Mechanism-based (suicide) inhibitor

Q8. Which experimental system best preserves cellular architecture and phase I plus phase II capacity for in vitro metabolism studies?

• Recombinant CYP microsomes
• Human liver microsomes
• Primary human hepatocytes
• Bacterial expression systems

Correct Answer: Primary human hepatocytes

Q9. What is the primary reactive metabolite formed from acetaminophen responsible for hepatotoxicity?

• NAPQI (N-acetyl-p-benzoquinone imine)
• Glutathione conjugate
• Acetylated metabolite
• Hydroxy-acetaminophen

Correct Answer: NAPQI (N-acetyl-p-benzoquinone imine)

Q10. Which Phase I reaction commonly leads to increased water solubility by converting lipophilic groups to polar groups?

• Oxidation
• Glucuronidation
• Sulfation
• Methylation

Correct Answer: Oxidation

Q11. CYP2D6 polymorphism often results in which clinical consequence?

• Uniform metabolism in all populations
• Variable metabolism leading to poor or ultra-rapid metabolizer phenotypes
• Enhanced glucuronidation only
• No impact on drug clearance

Correct Answer: Variable metabolism leading to poor or ultra-rapid metabolizer phenotypes

Q12. Which assay is commonly used to assess CYP activity using known probe substrates?

• ELISA for albumin
• Probe substrate assay with LC-MS detection
• Immunohistochemistry
• Genomic PCR for transporter genes

Correct Answer: Probe substrate assay with LC-MS detection

Q13. Flavin-containing monooxygenases (FMOs) mainly catalyze which type of reaction?

• N- and S-oxidation of nucleophilic heteroatoms
• Glucuronidation of phenols
• Peptide bond hydrolysis
• Reductive dehalogenation

Correct Answer: N- and S-oxidation of nucleophilic heteroatoms

Q14. Which parameter represents the substrate concentration at which reaction velocity is half of Vmax in Michaelis–Menten kinetics?

• kcat
• Km
• CLint
• IC50

Correct Answer: Km

Q15. Which metabolic reaction often results in removal of a methyl or alkyl group attached to nitrogen or oxygen?

• Dealkylation
• Decarboxylation
• Conjugation
• Oxidative coupling

Correct Answer: Dealkylation

Q16. Which of the following is a common non-P450 Phase I enzyme involved in alcohol metabolism?

• Monoamine oxidase
• Alcohol dehydrogenase
• Thiopurine methyltransferase
• UDP-glucuronosyltransferase

Correct Answer: Alcohol dehydrogenase

Q17. Grapefruit juice primarily affects which metabolic process?

• Induction of renal transporters
• Inhibition of intestinal CYP3A4 and P-gp leading to increased bioavailability
• Activation of hepatic glucuronidation
• Enhancement of biliary excretion

Correct Answer: Inhibition of intestinal CYP3A4 and P-gp leading to increased bioavailability

Q18. Which term describes the creation of a more reactive intermediate that can bind to macromolecules and cause toxicity?

• Detoxification
• Bioactivation
• Conjugation
• Elimination

Correct Answer: Bioactivation

Q19. Which of the following is NOT a typical Phase I metabolic reaction?

• Hydroxylation
• Oxidation
• Glucuronidation
• Reduction

Correct Answer: Glucuronidation

Q20. Which substrate preference differentiates CYP2C9 from CYP2C19?

• CYP2C9 prefers acidic drugs while CYP2C19 prefers basic drugs
• CYP2C9 metabolizes only steroids while CYP2C19 does not
• Both have identical substrate specificity
• CYP2C19 exclusively metabolizes peptides

Correct Answer: CYP2C9 prefers acidic drugs while CYP2C19 prefers basic drugs

Q21. Which experimental preparation is enriched for ER-bound CYP enzymes and used in many in vitro metabolism studies?

• Plasma fractions
• Microsomes
• Crude mitochondrial pellets
• Nuclear extracts

Correct Answer: Microsomes

Q22. Which clinical strategy can reduce formation of a toxic reactive metabolite from a drug?

• Co-administration with enzyme inducers
• Co-administration with inhibitors of the bioactivating enzyme
• Increasing drug dose
• Administering drug via inhalation exclusively

Correct Answer: Co-administration with inhibitors of the bioactivating enzyme

Q23. Stereoselective metabolism leads to which phenomenon?

• Both enantiomers are metabolized equally
• Different enantiomers are metabolized at different rates producing different pharmacokinetics
• Stereochemistry never affects metabolism
• Only racemic mixtures are metabolized

Correct Answer: Different enantiomers are metabolized at different rates producing different pharmacokinetics

Q24. Which is a common clinical consequence of CYP inhibition by a co-administered drug?

• Decreased plasma levels of the substrate drug
• No change in drug exposure
• Increased plasma levels of the substrate drug and potential toxicity
• Immediate renal elimination of the substrate

Correct Answer: Increased plasma levels of the substrate drug and potential toxicity

Q25. Which enzyme catalyzes deamination of monoamines and is important for neurotransmitter metabolism rather than typical drug Phase I metabolism?

• Monoamine oxidase (MAO)
• Cytochrome P450 3A4
• UDP-glucuronosyltransferase
• Glutathione S-transferase

Correct Answer: Monoamine oxidase (MAO)

Q26. Which factor most influences intrinsic clearance (CLint) of a drug in vitro?

• Plasma protein binding only
• Enzyme concentration and substrate affinity (Vmax and Km)
• Drug taste
• Route of administration

Correct Answer: Enzyme concentration and substrate affinity (Vmax and Km)

Q27. Which reaction type is catalyzed by aldehyde dehydrogenase in ethanol metabolism?

• Oxidation of acetaldehyde to acetate
• Hydrolysis of ester bonds
• Conjugation to glucuronic acid
• Reduction of ketones

Correct Answer: Oxidation of acetaldehyde to acetate

Q28. Which statement best describes noncompetitive inhibition of a Phase I enzyme?

• Inhibitor competes with substrate for the active site raising Km
• Inhibitor binds a separate site decreasing Vmax without changing Km
• Inhibitor is converted to a product by the enzyme
• Inhibition can be overcome by increasing substrate concentration

Correct Answer: Inhibitor binds a separate site decreasing Vmax without changing Km

Q29. Epoxidation of aromatic compounds by CYP enzymes can lead to which result?

• Formation of stable, nonreactive metabolites only
• Formation of reactive epoxide intermediates that can bind DNA or proteins
• Immediate conjugation to sulfate in plasma
• Reduction to alcohols exclusively

Correct Answer: Formation of reactive epoxide intermediates that can bind DNA or proteins

Q30. Which substrate would most likely undergo N-oxidation rather than O-dealkylation?

• Aliphatic alcohol
• Tertiary aromatic amine
• Simple ether
• Carboxylic acid

Correct Answer: Tertiary aromatic amine

Q31. Which CYP isoform is predominantly involved in metabolism of codeine to morphine?

• CYP3A4
• CYP2D6
• CYP1A2
• CYP2E1

Correct Answer: CYP2D6

Q32. What is the significance of regioselectivity in Phase I metabolism?

• It determines the organ of excretion
• It determines which position on a molecule is metabolized, influencing activity and toxicity
• It only applies to Phase II reactions
• It dictates protein binding in plasma

Correct Answer: It determines which position on a molecule is metabolized, influencing activity and toxicity

Q33. Which method helps predict human hepatic clearance from in vitro microsomal data?

• Allometric scaling without metabolism data
• In vitro–in vivo extrapolation (IVIVE) using CLint and scaling factors
• Measuring taste and solubility only
• Clinical trials without preclinical studies

Correct Answer: In vitro–in vivo extrapolation (IVIVE) using CLint and scaling factors

Q34. Which Phase I enzyme is important for reducing nitro groups to amines under certain conditions?

• Nitroreductase
• CYP3A4
• UDP-glucuronosyltransferase
• Carboxylesterase

Correct Answer: Nitroreductase

Q35. Which of the following increases drug metabolism by inducing CYP enzymes?

• Rifampicin
• Ketoconazole
• Fluoxetine
• Grapefruit juice

Correct Answer: Rifampicin

Q36. Which analytical technique is most commonly used to identify metabolites formed in Phase I reactions?

• Light microscopy
• Liquid chromatography–mass spectrometry (LC-MS)
• Urine dipstick test
• pH titration

Correct Answer: Liquid chromatography–mass spectrometry (LC-MS)

Q37. Which factor does NOT typically affect hepatic phase I metabolism?

• Genetic polymorphisms of enzymes
• Co-administered enzyme inducers/inhibitors
• Dietary factors such as grapefruit juice
• Ambient room lighting

Correct Answer: Ambient room lighting

Q38. Which Phase I reaction often precedes Phase II conjugation by introducing a functional group for conjugation?

• Hydroxylation
• Glucuronidation
• Sulfation
• Acetylation

Correct Answer: Hydroxylation

Q39. Which drug is a classic example of a prodrug activated by CYP-mediated oxidation?

• Propranolol
• Enalapril (activated to enalaprilat)
• Aspirin
• Metformin

Correct Answer: Enalapril (activated to enalaprilat)

Q40. Which type of inhibition can be overcome by increasing substrate concentration?

• Noncompetitive inhibition
• Irreversible inhibition
• Competitive inhibition
• Mechanism-based inhibition

Correct Answer: Competitive inhibition

Q41. A drug metabolized primarily by CYP2C9 could show increased plasma concentration with co-administration of which inhibitor?

• Fluconazole
• Carbamazepine
• Rifampicin
• St. John’s Wort

Correct Answer: Fluconazole

Q42. Which Phase I enzyme activity can be assessed using testosterone 6β-hydroxylation as a probe?

• CYP1A2
• CYP2D6
• CYP3A4
• CYP2E1

Correct Answer: CYP3A4

Q43. Which structural change typically reduces a drug’s activity through Phase I metabolism?

• Introduction of a hydrophobic alkyl chain
• Formation of a polar hydroxylated metabolite that decreases receptor binding
• Methylation increasing lipophilicity
• Conversion to a prodrug

Correct Answer: Formation of a polar hydroxylated metabolite that decreases receptor binding

Q44. Which clinical test can be used to phenotype CYP2D6 activity in a patient?

• Urinary cortisol measurement
• Administration of dextromethorphan and measuring metabolite ratios
• Fasting blood glucose test
• Serum creatinine clearance only

Correct Answer: Administration of dextromethorphan and measuring metabolite ratios

Q45. Which reaction is catalyzed by carboxylesterases in drug metabolism?

• Hydrolysis of esters to alcohols and acids
• N-oxidation of tertiary amines
• Oxidative deamination of amines
• Glutathione conjugation

Correct Answer: Hydrolysis of esters to alcohols and acids

Q46. Which metabolic pathway is most likely to be involved when a nitroaromatic drug becomes reduced under anaerobic conditions in the gut?

• Oxidative demethylation in the liver
• Reduction by gut microbial enzymes
• Glucuronidation in plasma
• Sulfation in kidney

Correct Answer: Reduction by gut microbial enzymes

Q47. Which descriptor indicates the rate of product formation per enzyme active site under saturated substrate conditions?

• Km
• kcat
• IC50
• CLr

Correct Answer: kcat

Q48. Which is a limitation of using recombinant single CYP enzymes for metabolism studies?

• They perfectly replicate hepatic cofactor and protein interactions
• They lack the full complement of hepatic enzymes and cellular context influencing metabolism
• They are identical to primary hepatocytes in all aspects
• They cannot be used to study specific CYP isoforms

Correct Answer: They lack the full complement of hepatic enzymes and cellular context influencing metabolism

Q49. Which Phase I change would most likely increase a drug’s susceptibility to Phase II glucuronidation?

• Removal of hydroxyl groups
• Formation of polar groups like hydroxyl or carboxyl
• Methylation of phenolic OH
• Conversion to a more lipophilic form

Correct Answer: Formation of polar groups like hydroxyl or carboxyl

Q50. Which approach helps reduce variability in drug metabolism caused by genetic polymorphisms in a clinical setting?

• Ignoring genotype information
• Therapeutic drug monitoring and dose adjustment based on phenotype/genotype
• Prescribing standard doses for all patients
• Avoiding all drugs metabolized by CYP enzymes

Correct Answer: Therapeutic drug monitoring and dose adjustment based on phenotype/genotype

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

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