Phase I and Phase II metabolism MCQs With Answer

Phase I and Phase II metabolism MCQs With Answer

Phase I and Phase II metabolism are central topics in drug biotransformation for B.Pharm students. Phase I reactions (oxidation, reduction, hydrolysis) introduce or expose functional groups primarily via cytochrome P450 enzymes, altering drug polarity and activity. Phase II reactions (conjugation) couple metabolites with endogenous donors—glucuronidation, sulfation, acetylation, methylation, glutathione conjugation—to increase water solubility and promote excretion. Understanding enzyme families (CYPs, UGTs, SULTs, NATs, GSTs), cofactors (NADPH, UDPGA), genetic polymorphisms, induction/inhibition, and clinical consequences (drug interactions, bioactivation, toxic metabolites) is essential for pharmacokinetics, dosing, and patient safety. This focused set of MCQs emphasizes mechanistic details, clinical relevance, and problem-solving skills. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which organ and cell type are the primary site for both Phase I and Phase II drug metabolism?

• Liver (hepatocytes)
• Kidney (proximal tubule cells)
• Intestine (enterocytes)
• Plasma (blood cells)

Correct Answer: Liver (hepatocytes)

Q2. Which enzyme family is most responsible for Phase I oxidative metabolism of drugs?

• UDP-glucuronosyltransferases (UGTs)
• Cytosolic sulfotransferases (SULTs)
• Cytochrome P450 monooxygenases (CYPs)
• Glutathione S-transferases (GSTs)

Correct Answer: Cytochrome P450 monooxygenases (CYPs)

Q3. Which cofactor is essential for microsomal CYP-mediated oxidation reactions?

• UDP-glucuronic acid (UDPGA)
• NADPH
• S-adenosylmethionine (SAM)
• Glutathione (GSH)

Correct Answer: NADPH

Q4. Phase II glucuronidation is catalyzed by which enzyme family and where are these enzymes localized?

• UGTs localized in the endoplasmic reticulum
• SULTs localized in mitochondria
• NATs localized in lysosomes
• CYPs localized in the cytosol

Correct Answer: UGTs localized in the endoplasmic reticulum

Q5. Which Phase II reaction commonly detoxifies electrophilic reactive metabolites and protects against toxicity?

• Glucuronidation
• Sulfation
• Glutathione conjugation
• Methylation

Correct Answer: Glutathione conjugation

Q6. Which statement best describes a prodrug strategy involving Phase I metabolism?

• Administering a compound that is active and later inactivated by CYPs
• Using a precursor converted by Phase I enzymes into an active drug
• Giving a drug that undergoes direct conjugation without prior modification
• Designing a molecule that is excreted unchanged

Correct Answer: Using a precursor converted by Phase I enzymes into an active drug

Q7. Which genetic polymorphism is classically associated with altered metabolism of codeine to morphine?

• CYP3A4 ultrarapid metabolizer genotype
• CYP2D6 polymorphism
• UGT1A1*28 polymorphism
• NAT2 slow acetylator allele

Correct Answer: CYP2D6 polymorphism

Q8. Which conjugation reaction uses UDP-glucuronic acid as the co-substrate?

• Sulfation
• Glucuronidation
• Acetylation
• Methylation

Correct Answer: Glucuronidation

Q9. Which Phase I reaction type directly converts an ester drug into its corresponding acid and alcohol?

• Oxidation by CYP
• Reduction
• Hydrolysis by esterases
• Conjugation with sulfate

Correct Answer: Hydrolysis by esterases

Q10. Which factor most commonly causes clinically significant drug–drug interactions via metabolism?

• Renal elimination competition
• Enzyme induction or inhibition of CYPs
• Protein binding displacement only
• Age-related decreased absorption

Correct Answer: Enzyme induction or inhibition of CYPs

Q11. Which Phase II enzyme catalyzes acetylation and shows genetically determined slow and fast phenotypes?

• N-acetyltransferase (NAT)
• UDP-glucuronosyltransferase (UGT)
• Sulfotransferase (SULT)
• Glutathione S-transferase (GST)

Correct Answer: N-acetyltransferase (NAT)

Q12. Which of the following best describes enterohepatic recycling?

• Repeated renal reabsorption of the drug
• Conjugated drug secreted in bile, hydrolyzed in gut, and reabsorbed
• Hepatic uptake and immediate urinary excretion
• Drug binding to plasma proteins and slow release

Correct Answer: Conjugated drug secreted in bile, hydrolyzed in gut, and reabsorbed

Q13. Which CYP isoform is responsible for metabolism of the largest proportion of marketed drugs?

• CYP1A2
• CYP2C9
• CYP2D6
• CYP3A4

Correct Answer: CYP3A4

Q14. Which of the following is a common Phase II reaction that can result in decreased pharmacologic activity due to loss of binding affinity?

• Methylation
• Glucuronidation
• Acetylation
• Sulfation

Correct Answer: Glucuronidation

Q15. Which concept explains increased enzyme expression after chronic exposure to certain drugs (e.g., rifampicin increases CYP3A4)?

• Enzyme inhibition
• Enzyme induction
• Enzyme saturation
• Competitive antagonism

Correct Answer: Enzyme induction

Q16. Which metabolite formation is an example of bioactivation producing a toxic species (e.g., acetaminophen toxicity)?

• Glucuronide conjugate of acetaminophen
• Sulfate conjugate of acetaminophen
• NAPQI produced by CYP-mediated oxidation
• Methylated inactive acetaminophen

Correct Answer: NAPQI produced by CYP-mediated oxidation

Q17. Which analytical parameter describes the maximum rate of an enzyme-catalyzed metabolic reaction?

• Km (Michaelis constant)
• Vmax
• Clearance (Cl)
• Half-life (t1/2)

Correct Answer: Vmax

Q18. Which Phase II pathway commonly competes with glucuronidation at high substrate concentrations for drugs with phenolic groups?

• Sulfation
• Methylation
• Acetylation
• Glutathione conjugation

Correct Answer: Sulfation

Q19. Which statement about first-pass metabolism is correct?

• It reduces oral bioavailability by hepatic and intestinal metabolism before systemic circulation
• It enhances systemic drug levels by activating prodrugs only
• It occurs exclusively in the kidneys
• It refers to metabolic clearance after intravenous administration

Correct Answer: It reduces oral bioavailability by hepatic and intestinal metabolism before systemic circulation

Q20. Which enzyme family catalyzes addition of glutathione to electrophilic drug metabolites?

• Sulfotransferases (SULTs)
• Glutathione S-transferases (GSTs)
• UDP-glucuronosyltransferases (UGTs)
• Cytochrome P450s (CYPs)

Correct Answer: Glutathione S-transferases (GSTs)

Q21. Slow acetylators (NAT2) are at increased risk of which adverse effect with isoniazid therapy?

• Hepatotoxicity due to NAPQI
• Peripheral neuropathy and lupus-like syndrome
• Renal failure from crystal deposition
• Excessive sedation

Correct Answer: Peripheral neuropathy and lupus-like syndrome

Q22. Which drug interaction results from competitive inhibition at the same CYP isoform and can raise plasma levels of a substrate drug?

• Enzyme induction by rifampicin
• CYP inhibition by ketoconazole
• Increased renal clearance by probenecid
• Protein binding displacement by aspirin

Correct Answer: CYP inhibition by ketoconazole

Q23. Which Phase I reaction typically decreases a drug’s lipophilicity and increases polarity?

• Methylation
• Oxidation (e.g., hydroxylation)
• Acetylation
• Mannich reaction

Correct Answer: Oxidation (e.g., hydroxylation)

Q24. Which conjugation reaction uses PAPS (3′-phosphoadenosine-5′-phosphosulfate) as the sulfate donor?

• Glucuronidation
• Sulfation by SULT enzymes
• Acetylation
• Methylation by COMT

Correct Answer: Sulfation by SULT enzymes

Q25. Which pharmacokinetic parameter directly depends on both hepatic blood flow and intrinsic clearance (well-stirred model)?

• Volume of distribution
• Hepatic clearance
• Absorption rate constant
• Renal filtration rate

Correct Answer: Hepatic clearance

Q26. Which clinical scenario is most likely if a patient is an ultrarapid CYP2D6 metabolizer given standard codeine dosing?

• Poor analgesia due to lack of conversion
• Increased toxicity from rapid conversion to morphine
• Unchanged response compared with normal metabolizers
• Decreased risk of opioid side effects

Correct Answer: Increased toxicity from rapid conversion to morphine

Q27. Which of the following is a characteristic of Phase II reactions compared with Phase I?

• They always generate reactive electrophiles
• They increase water solubility by adding endogenous groups
• They are primarily catalyzed by CYP enzymes
• They generally decrease clearance

Correct Answer: They increase water solubility by adding endogenous groups

Q28. Which laboratory approach is commonly used to phenotype CYP activity in vivo using probe drugs?

• Urine immunoassay for metabolites only
• Administering a specific probe substrate and measuring metabolic ratio
• Measuring plasma protein binding exclusively
• Assessing blood pressure changes after drug dosing

Correct Answer: Administering a specific probe substrate and measuring metabolic ratio

Q29. Which drug clearance mechanism is most affected by severe hepatic impairment?

• Glomerular filtration of hydrophilic drugs
• Metabolic clearance via hepatic enzymes
• Intestinal absorption rate
• Exhalation of volatile anesthetics only

Correct Answer: Metabolic clearance via hepatic enzymes

Q30. Which cofactor provides the glucuronic acid moiety for UDP-glucuronosyltransferase reactions?

• UDP-N-acetylglucosamine
• UDP-glucuronic acid (UDPGA)
• NADH
• S-adenosylmethionine (SAM)

Correct Answer: UDP-glucuronic acid (UDPGA)

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.

Mail- Sachin@pharmacyfreak.com