Urea cycle MCQs With Answer

Urea cycle MCQs With Answer are essential study aids for B. Pharm students preparing for biochemistry, pharmacology, and clinical exams. This focused set covers enzyme names, reaction steps, mitochondrial versus cytosolic localization, regulation by N-acetylglutamate, energy cost, and clinical aspects such as hyperammonemia and ornithine transcarbamylase deficiency. Each question reinforces core concepts like ammonia detoxification, carbamoyl phosphate synthesis, argininosuccinate formation, and links to the TCA cycle. Ideal for revision, practice tests, and exam readiness, these MCQs clarify mechanisms and therapeutic approaches including amino acid supplementation and ammonia-scavenging drugs. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which enzyme catalyzes the first committed step of the urea cycle?

• Ornithine transcarbamylase
• Arginase
• Carbamoyl phosphate synthetase I
• Argininosuccinate synthase

Correct Answer: Carbamoyl phosphate synthetase I

Q2. Where is carbamoyl phosphate synthetase I located in the cell?

• Cytosol
• Mitochondrial matrix
• Endoplasmic reticulum
• Golgi apparatus

Correct Answer: Mitochondrial matrix

Q3. What is the allosteric activator required for optimal activity of carbamoyl phosphate synthetase I?

• Arginine
• N-acetylglutamate
• Glutamine

Correct Answer: N-acetylglutamate

Q4. Which amino acid is directly produced by hydrolysis of arginine in the final step of the urea cycle?

• Ornithine
• Urea
• Citrulline
• Argininosuccinate

Correct Answer: Ornithine

Q5. Which intermediate links the urea cycle to the TCA cycle?

• Fumarate
• Malate
• Oxaloacetate
• Succinate

Correct Answer: Fumarate

Q6. Which enzyme converts ornithine and carbamoyl phosphate to citrulline?

• Arginase
• Argininosuccinate lyase
• Ornithine transcarbamylase
• Carbamoyl phosphate synthetase II

Correct Answer: Ornithine transcarbamylase

Q7. How many high-energy phosphate bonds (ATP equivalents) are consumed per urea molecule synthesized?

• 1
• 2
• 3
• 4

Correct Answer: 4

Q8. Which urea cycle enzyme deficiency classically presents with elevated orotic acid in urine?

• Carbamoyl phosphate synthetase I deficiency
• Ornithine transcarbamylase deficiency
• Arginase deficiency
• Argininosuccinate lyase deficiency

Correct Answer: Ornithine transcarbamylase deficiency

Q9. What is the immediate nitrogen donor for carbamoyl phosphate synthesis by CPS I?

• Glutamine
• Free ammonia (NH4+)
• Nitrite
• Urea

Correct Answer: Free ammonia (NH4+)

Q10. Which urea cycle enzyme is localized in the cytosol rather than mitochondria?

• Carbamoyl phosphate synthetase I
• Ornithine transcarbamylase
• Argininosuccinate synthase
• Carbamoyl phosphate synthetase II

Correct Answer: Argininosuccinate synthase

Q11. Which cofactor is essential for argininosuccinate synthase activity?

• NAD+
• ATP
• Pyridoxal phosphate
• Biotin

Correct Answer: ATP

Q12. Argininosuccinate is cleaved to form arginine and which other molecule?

• Citrulline
• Fumarate
• Malate
• Succinate

Correct Answer: Fumarate

Q13. N-acetylglutamate synthase deficiency produces symptoms due to impaired activation of which enzyme?

• Arginase
• Carbamoyl phosphate synthetase I
• Ornithine transcarbamylase
• Argininosuccinate lyase

Correct Answer: Carbamoyl phosphate synthetase I

Q14. In adults, what is the primary tissue responsible for the full urea cycle?

• Kidney
• Intestine
• Liver
• Muscle

Correct Answer: Liver

Q15. Which of the following increases urea cycle activity by providing substrate nitrogen from amino acid catabolism?

• Fasting
• High-carbohydrate meal
• Insulin infusion
• Refeeding after starvation

Correct Answer: Fasting

Q16. Which transporter moves ornithine into the mitochondrial matrix in the urea cycle?

• Ornithine translocase
• Ornithine aminotransferase
• Ornithine decarboxylase
• Urea transporter

Correct Answer: Ornithine translocase

Q17. Which genetic inheritance pattern is most common for ornithine transcarbamylase (OTC) deficiency?

• Autosomal dominant
• X-linked recessive
• Autosomal recessive
• Mitochondrial inheritance

Correct Answer: X-linked recessive

Q18. Elevated blood ammonia primarily affects which organ leading to encephalopathy?

• Heart
• Liver
• Kidney
• Brain

Correct Answer: Brain

Q19. Which clinical sign is commonly associated with hyperammonemia in neonates?

• Hypotonia and poor feeding
• Hyperreflexia and hypertension
• Dark urine and jaundice
• Muscle hypertrophy

Correct Answer: Hypotonia and poor feeding

Q20. Sodium benzoate treats hyperammonemia by promoting excretion of nitrogen as which conjugate?

• Phenylacetylglutamine
• Hippurate (benzoyl glycine)
• Urea
• Uric acid

Correct Answer: Hippurate (benzoyl glycine)

Q21. Phenylbutyrate lowers ammonia by generating which active metabolite that conjugates glutamine?

• Phenylacetate
• Benzoate
• Phenylalanine
• PABA

Correct Answer: Phenylacetate

Q22. Which laboratory test is most useful to differentiate CPS I deficiency from OTC deficiency?

• Serum urea level
• Plasma citrulline and urinary orotic acid levels
• Plasma glucose
• Serum creatinine

Correct Answer: Plasma citrulline and urinary orotic acid levels

Q23. Which amino acid supplementation may be given to urea cycle disorder patients to promote alternative nitrogen excretion?

• Lysine
• Arginine
• Proline
• Glycine

Correct Answer: Arginine

Q24. Carbamoyl phosphate synthetase II differs from CPS I by using which nitrogen donor?

• Free ammonia
• Glutamine
• Asparagine
• Arginine

Correct Answer: Glutamine

Q25. Arginase deficiency typically causes accumulation of which amino acid?

• Arginine
• Ornithine
• Citrulline
• Glutamine

Correct Answer: Arginine

Q26. The synthesis of carbamoyl phosphate by CPS I requires which substrates?

• Ammonia, bicarbonate, and ATP
• Nitrite, ATP, and NADH
• Glutamate, CO2, and GTP
• Ornithine, citrulline, and ATP

Correct Answer: Ammonia, bicarbonate, and ATP

Q27. Which enzyme deficiency causes argininosuccinic aciduria with hepatomegaly and neurodevelopmental delay?

• Argininosuccinate synthase deficiency
• Arginase deficiency
• Argininosuccinate lyase deficiency
• Ornithine transcarbamylase deficiency

Correct Answer: Argininosuccinate lyase deficiency

Q28. Citrullinemia type I is due to deficiency of which enzyme?

• Argininosuccinate lyase
• Argininosuccinate synthase
• Ornithine transcarbamylase
• Carbamoyl phosphate synthetase I

Correct Answer: Argininosuccinate synthase

Q29. Which metabolite accumulates in OTC deficiency leading to increased urinary orotic acid?

• Carbamoyl phosphate
• Argininosuccinate
• Urea
• Fumarate

Correct Answer: Carbamoyl phosphate

Q30. Which of the following is NOT a function of the urea cycle?

• Detoxification of ammonia
• Synthesis of arginine
• Generation of glucose from ammonia
• Linking nitrogen metabolism to TCA cycle

Correct Answer: Generation of glucose from ammonia

Q31. In which compartment does the conversion of citrulline to argininosuccinate occur?

• Mitochondrial matrix
• Cytosol
• Endoplasmic reticulum lumen
• Inner mitochondrial membrane

Correct Answer: Cytosol

Q32. Which enzyme releases urea from arginine to complete the cycle?

• Arginase
• Argininosuccinate synthetase
• Argininosuccinate lyase
• Ornithine carbamoyltransferase

Correct Answer: Arginase

Q33. Which metabolite produced by the urea cycle is used in nitric oxide synthesis?

• Ornithine
• Arginine
• Citrulline
• Fumarate

Correct Answer: Arginine

Q34. Which step in the urea cycle directly consumes two molecules of ATP?

• Conversion of citrulline to argininosuccinate
• Synthesis of carbamoyl phosphate by CPS I
• Hydrolysis of arginine by arginase
• Cleavage of argininosuccinate to fumarate and arginine

Correct Answer: Synthesis of carbamoyl phosphate by CPS I

Q35. Which regulatory condition increases N-acetylglutamate synthesis, thereby stimulating CPS I?

• Low-protein diet
• High-protein diet or increased amino acid catabolism
• Hypothermia
• Hyperinsulinemia

Correct Answer: High-protein diet or increased amino acid catabolism

Q36. Which disease is associated with episodic hyperammonemia triggered by catabolic stress?

• Phenylketonuria
• Urea cycle disorders like OTC deficiency
• Type II diabetes
• Hemochromatosis

Correct Answer: Urea cycle disorders like OTC deficiency

Q37. What is the fate of fumarate produced in the urea cycle?

• Converted to malate and enters the TCA cycle
• Directly excreted in urine
• Converted to succinyl-CoA
• Used for fatty acid synthesis

Correct Answer: Converted to malate and enters the TCA cycle

Q38. Which enzyme deficiency results in hyperargininemia presenting in childhood with spasticity and growth retardation?

• Arginase deficiency
• Ornithine transcarbamylase deficiency
• Carbamoyl phosphate synthetase I deficiency
• Argininosuccinate synthase deficiency

Correct Answer: Arginase deficiency

Q39. Which laboratory finding is typical in severe urea cycle disorders?

• Hypoammonemia
• Marked hyperammonemia with low BUN (blood urea nitrogen)
• High BUN and low ammonia
• Elevated serum creatine kinase

Correct Answer: Marked hyperammonemia with low BUN (blood urea nitrogen)

Q40. Which step in the urea cycle occurs in the mitochondrion?

• Conversion of argininosuccinate to arginine and fumarate
• Synthesis of arginine from citrulline
• Carbamoyl phosphate synthesis and formation of citrulline from ornithine
• Hydrolysis of arginine to urea

Correct Answer: Carbamoyl phosphate synthesis and formation of citrulline from ornithine

Q41. Which molecule provides the carbonyl group in carbamoyl phosphate synthesized by CPS I?

• Carbon dioxide (as bicarbonate)
• Carbon monoxide
• Formate
• Acetyl-CoA

Correct Answer: Carbon dioxide (as bicarbonate)

Q42. Which therapeutic approach is used acutely for severe hyperammonemia?

• High-protein diet
• Dialysis to remove ammonia
• Oral arginine only
• Administration of ammonium chloride

Correct Answer: Dialysis to remove ammonia

Q43. Which amino transfer reaction supplies ammonia for urea synthesis during amino acid catabolism?

• Transamination producing glutamate followed by glutamate dehydrogenase releasing ammonia
• Decarboxylation of amino acids
• Direct deamination of lysine
• Conversion of proline to hydroxyproline

Correct Answer: Transamination producing glutamate followed by glutamate dehydrogenase releasing ammonia

Q44. Which condition can lead to secondary hyperammonemia by impairing urea cycle enzyme function?

• Liver failure
• Hypothyroidism
• Vitamin C deficiency
• Renal tubular acidosis

Correct Answer: Liver failure

Q45. What is the common initial biochemical abnormality in neonates with urea cycle defects?

• Hypoglycemia
• Severe hyperammonemia
• Metabolic alkalosis
• High plasma urea

Correct Answer: Severe hyperammonemia

Q46. Which compound is used diagnostically to test for OTC deficiency due to accumulation in orotic acid pathway?

• Urinary orotic acid measurement
• Plasma lactate measurement
• Serum ferritin measurement
• Urinary ketone bodies

Correct Answer: Urinary orotic acid measurement

Q47. Which of the following enzymes is biochemically linked to nitric oxide synthase through arginine metabolism?

• Arginase competing for arginine substrate
• Ornithine transcarbamylase producing citrulline
• Carbamoyl phosphate synthetase I producing carbamoyl phosphate
• Argininosuccinate synthase producing fumarate

Correct Answer: Arginase competing for arginine substrate

Q48. In the context of urea cycle, which amino acid can be recycled from citrulline in the kidney to aid in nitric oxide production systemically?

• Glutamine
• Arginine
• Lysine
• Leucine

Correct Answer: Arginine

Q49. Which metabolic demand increases urea synthesis rate most markedly?

• High carbohydrate intake
• High-protein diet or increased proteolysis
• Prolonged exercise without protein intake
• Fasting with glucose infusion

Correct Answer: High-protein diet or increased proteolysis

Q50. Which statement best describes the clinical utility of knowing urea cycle MCQs for B. Pharm students?

• They are only relevant for basic science courses and not clinical therapeutics
• They help understand biochemical basis of hyperammonemia, guide drug therapy and dosing, and link pharmacology to metabolism
• They replace the need to study pharmacokinetics
• They are irrelevant to drug development and toxicology

Correct Answer: They help understand biochemical basis of hyperammonemia, guide drug therapy and dosing, and link pharmacology to metabolism

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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