Therapeutic applications of enzymes MCQs With Answer

Introduction

This question set on the therapeutic applications of enzymes is tailored for M.Pharm students studying Advanced Pharmaceutical Biotechnology. It reviews clinically important enzyme therapies, mechanisms of action, formulation and delivery challenges, immunogenicity, and strategies to improve enzyme pharmacokinetics and targeting. The MCQs are designed to deepen understanding beyond basic facts by addressing practical considerations in development and clinical use — such as glycosylation, PEGylation, lysosomal targeting, enzyme prodrug strategies, and monitoring of enzyme therapy. Use these items for self-assessment, exam preparation, and to stimulate further reading on enzyme-based therapeutics and their role in modern pharmacotherapy.

Q1. Which mechanism best describes how tissue plasminogen activator (tPA) exerts its therapeutic effect in acute ischemic stroke?

• Directly cleaves fibrinogen into fibrin to form stable clots
• Converts plasminogen to plasmin which degrades fibrin clots
• Inhibits platelet aggregation by blocking ADP receptors
• Activates antithrombin III to inhibit thrombin

Correct Answer: Converts plasminogen to plasmin which degrades fibrin clots

Q2. Which of the following enzymes is used as enzyme replacement therapy for Gaucher disease?

• Alglucosidase alfa
• Imiglucerase
• Rasburicase
• Asparaginase

Correct Answer: Imiglucerase

Q3. PEGylation of therapeutic enzymes is primarily used to:

• Increase catalytic activity by altering active site geometry
• Protect the enzyme from proteolysis and reduce immunogenicity, prolonging plasma half-life
• Change substrate specificity to broaden clinical uses
• Enable oral bioavailability by promoting gut absorption

Correct Answer: Protect the enzyme from proteolysis and reduce immunogenicity, prolonging plasma half-life

Q4. Which therapeutic enzyme is specifically indicated for lowering plasma uric acid in refractory gout by catalyzing uric acid to allantoin?

• Alglucosidase alfa
• Pegloticase
• Dornase alfa
• Thrombolytic streptokinase

Correct Answer: Pegloticase

Q5. Which glycosylation-related modification is critical for targeting recombinant lysosomal enzymes to the lysosome after systemic administration?

• Mannose-6-phosphate residues on N-linked glycans
• Sialylation of O-linked glycans
• High-mannose glycosylation for hepatic clearance
• Fucose addition to increase plasma half-life

Correct Answer: Mannose-6-phosphate residues on N-linked glycans

Q6. Which adverse effect is most commonly associated with L-asparaginase therapy in acute lymphoblastic leukemia?

• Hypoglycemia due to insulin-like activity
• Hepatotoxicity, pancreatitis, and coagulopathy due to protein synthesis impairment
• Renal tubular acidosis due to enzyme accumulation
• Severe hyperkalemia from cellular lysis

Correct Answer: Hepatotoxicity, pancreatitis, and coagulopathy due to protein synthesis impairment

Q7. Dornase alfa (rhDNase) is used therapeutically in cystic fibrosis primarily because it:

• Hydrolyzes mucin glycoproteins to thin secretions
• Cleaves extracellular DNA to reduce sputum viscosity
• Stimulates chloride transport across airway epithelia
• Acts as an antibiotic by breaking bacterial cell walls

Correct Answer: Cleaves extracellular DNA to reduce sputum viscosity

Q8. Which factor is most critical when designing a formulation to stabilize a therapeutic enzyme for parenteral administration?

• Selection of an inert oral matrix to prevent degradation in the stomach
• Optimization of buffer pH, excipients (e.g., sugars, amino acids) and control of aggregation
• Incorporation of proteolytic enzymes to activate the therapeutic enzyme
• Use of strong oxidizing agents to maintain enzyme structure

Correct Answer: Optimization of buffer pH, excipients (e.g., sugars, amino acids) and control of aggregation

Q9. Which statement correctly contrasts streptokinase and tissue plasminogen activator (tPA)?

• Streptokinase is a fibrin-specific activator while tPA activates plasminogen systemically
• Streptokinase forms a complex with plasminogen to activate it and is more antigenic than tPA
• Both have identical immunogenic profiles and half-lives
• tPA is a bacterial protein with high antigenicity compared to streptokinase

Correct Answer: Streptokinase forms a complex with plasminogen to activate it and is more antigenic than tPA

Q10. Which enzyme is used for enzymatic debridement of chronic wounds and pressure ulcers?

• Collagenase
• Rasburicase
• Pegloticase
• Dornase alfa

Correct Answer: Collagenase

Q11. In enzyme prodrug therapy for cancer, the primary goal is to:

• Deliver a fully active enzyme systemically to degrade tumor stroma
• Target an enzyme to the tumor that will locally convert a non-toxic prodrug into a cytotoxic drug
• Replace deficient enzymes in tumor cells to restore normal metabolism
• Use enzymes to enhance immune checkpoint blockade

Correct Answer: Target an enzyme to the tumor that will locally convert a non-toxic prodrug into a cytotoxic drug

Q12. Which therapeutic enzyme is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolysis?

• Asparaginase
• Rasburicase
• Alglucosidase alfa
• Imiglucerase

Correct Answer: Rasburicase

Q13. What is the primary reason recombinant therapeutic enzymes produced in bacteria often require additional processing compared to those produced in mammalian cells?

• Bacterial systems over-glycosylate proteins leading to hyperactivity
• Bacterial expression lacks mammalian post-translational modifications such as glycosylation, affecting stability and targeting
• Bacterial expression inherently produces humanized glycoforms
• Proteins from bacteria have prolonged half-life and do not require PEGylation

Correct Answer: Bacterial expression lacks mammalian post-translational modifications such as glycosylation, affecting stability and targeting

Q14. Which monitoring parameter is most relevant during ongoing therapy with systemic thrombolytic enzymes?

• Serum creatinine only
• Coagulation profile (e.g., fibrinogen, PT, aPTT) and signs of bleeding
• Blood glucose and HbA1c
• Serum uric acid levels exclusively

Correct Answer: Coagulation profile (e.g., fibrinogen, PT, aPTT) and signs of bleeding

Q15. Which strategy is commonly used to reduce immune responses to therapeutic enzymes administered chronically?

• Administering escalating oral doses to induce central tolerance
• Co-administration of immunosuppressive agents or use of PEGylation and glycoengineering to mask epitopes
• Frequent high-dose bolus injections to overwhelm the immune system
• Using only bacterial enzymes which are less immunogenic

Correct Answer: Co-administration of immunosuppressive agents or use of PEGylation and glycoengineering to mask epitopes

Q16. Which enzyme is used in Pompe disease as enzyme replacement therapy?

• Alglucosidase alfa
• Imiglucerase
• Asparaginase
• Dornase alfa

Correct Answer: Alglucosidase alfa

Q17. Which property of an enzyme preparation most directly influences its tissue distribution after intravenous administration?

• Substrate specificity
• Molecular size and presence of targeting ligands (e.g., M6P tags)
• Enzymatic turnover number (kcat)
• Color and odor of the formulation

Correct Answer: Molecular size and presence of targeting ligands (e.g., M6P tags)

Q18. Which of the following is a major regulatory concern when approving biosimilar therapeutic enzymes?

• Exact nucleotide sequence identity between biosimilar and originator
• Demonstration of similar quality attributes, pharmacokinetics, efficacy, and immunogenicity profiles
• Use of identical cell bank and manufacturing equipment as the originator
• Lower cost irrespective of clinical comparability

Correct Answer: Demonstration of similar quality attributes, pharmacokinetics, efficacy, and immunogenicity profiles

Q19. Which enzyme is used therapeutically to treat exocrine pancreatic insufficiency?

• Pancrelipase (mixture of lipases, proteases and amylases)
• Rasburicase
• Pegloticase
• Thrombolytic tPA

Correct Answer: Pancrelipase (mixture of lipases, proteases and amylases)

Q20. Which analytical test is essential for potency specification of a therapeutic enzyme product?

• Total protein by Lowry assay only
• Functional enzymatic activity assay that measures catalytic conversion of substrate under defined conditions
• Visual inspection for color changes only
• Measurement of endotoxin without activity assessment

Correct Answer: Functional enzymatic activity assay that measures catalytic conversion of substrate under defined conditions

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