Amino Acid Metabolism and Urea Cycle (Disorders, Phenylketonuria) MCQs

Biochemistry · 102 free questions with answers & explanations.

1. A neonate is screened positive for phenylketonuria (PKU) on the Guthrie bacterial inhibition assay. Phenylalanine hydroxylase is absent. Which cofactor is absolutely required for phenylalanine hydroxylase activity, and its deficiency causes a variant 'malignant' form of hyperphenylalaninemia?
2. The urea cycle converts toxic ammonia into urea for renal excretion. Which enzyme deficiency in the urea cycle results in orotic aciduria along with hyperammonemia?
3. A 2-year-old child presents with fair skin, blue eyes, musty body odor, intellectual disability, and seizures. Urine ferric chloride test gives a green color. Which metabolite is responsible for the musty odor?
4. A homozygous infant with maple syrup urine disease (MSUD) presents at day 5 of life with poor feeding, maple syrup-smelling urine, and encephalopathy. The enzyme defective in MSUD is:
5. A 10-day-old neonate is brought with lethargy, poor feeding, and vomiting after protein feeds. Plasma amino acid profile shows marked elevation of citrulline with low argininosuccinate. Urinary orotic acid is elevated. The enzyme deficiency most consistent with this presentation is:
6. Classic phenylketonuria (PKU) results from phenylalanine hydroxylase (PAH) deficiency. In addition to intellectual disability from phenylalanine accumulation, patients develop a musty/mousy urine odor due to accumulation of phenylacetate and phenyllactate. Which coenzyme required by PAH is also a cofactor for tyrosine hydroxylase and tryptophan hydroxylase?
7. A 2-year-old with maple syrup urine disease (MSUD) presents in metabolic crisis. Plasma shows elevated leucine, isoleucine, and valine with their respective keto acids. The enzyme complex deficient in MSUD is structurally homologous to which other mitochondrial enzyme complex?
8. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency presents with lens dislocation (downward/inward), intellectual disability, osteoporosis, and thromboembolic events. Pyridoxine (B6) supplementation helps approximately 50% of patients because:
9. N-acetylglutamate (NAG) is an essential allosteric activator of carbamoyl phosphate synthetase-I (CPS-I), the first committed step of the urea cycle. Which amino acid's catabolism generates acetyl-CoA that is used by NAG synthase to produce NAG?
10. A newborn with urea cycle defect presents with hyperammonemia on day 2. Plasma citrulline is markedly elevated, but argininosuccinate is absent. Argininosuccinic aciduria is ruled out. Which enzyme defect best explains this biochemical pattern?
11. Classic PKU (phenylalanine hydroxylase deficiency) causes intellectual disability when untreated. Sapropterin (BH4 — tetrahydrobiopterin) therapy benefits ~25% of PKU patients. What is the molecular basis for this selective BH4 responsiveness?
12. Maple syrup urine disease (MSUD) results from deficiency of the branched-chain alpha-ketoacid dehydrogenase complex. Which specific biochemical mechanism leads to the neurological crisis if not treated promptly?
13. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency causes intellectual disability, ectopia lentis (downward), marfanoid habitus, and thromboembolic events. Pyridoxine (B6) supplementation helps ~50% of patients. What is the biochemical rationale?
14. Alkaptonuria (homogentisate 1,2-dioxygenase deficiency) is a rare autosomal recessive disorder of tyrosine catabolism. A 45-year-old presents with ochronosis (dark pigmentation of cartilage) and arthropathy. Which biochemical mechanism causes the connective tissue damage?
15. A newborn male is detected on neonatal screening with elevated plasma citrulline (1200 micromol/L; normal <40) and ammonia (350 micromol/L). Argininosuccinate is absent in urine. Urine orotic acid is markedly elevated. Which enzyme defect is MOST consistent with this pattern?
16. A 6-year-old presents with progressive intellectual disability, fair complexion, musty odor, and eczema. Plasma phenylalanine is 1400 micromol/L. Phenylalanine hydroxylase (PAH) activity is <1% of normal. The patient is started on sapropterin (BH4 analogue). Sapropterin would be expected to benefit which specific subset of PKU patients?
17. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is treated with pyridoxine (vitamin B6) in responsive patients. CBS catalyzes the condensation of homocysteine with serine to form cystathionine. In the trans-sulfuration pathway, the sulfur atom originally from methionine appears in which final product?
18. A child with maple syrup urine disease (MSUD) is in metabolic crisis with encephalopathy and plasma leucine of 2800 micromol/L. The branched-chain alpha-keto acid dehydrogenase (BCKD) complex has a structure analogous to pyruvate dehydrogenase. Which cofactor common to both BCKD and pyruvate dehydrogenase is absent in this child's diet that could trigger a MSUD-like biochemical crisis even in a dietary-compliant patient?
19. Propionic acidemia results from propionyl-CoA carboxylase deficiency. This enzyme uses biotin and converts propionyl-CoA to methylmalonyl-CoA. A separate patient has methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency. Both patients accumulate odd-chain fatty acids in their tissues. Propionic acid is also produced from the catabolism of which four amino acids?
20. A 3-year-old child presents with progressive intellectual disability, seizures, and intermittent episodes of encephalopathy triggered by high-protein meals. Plasma amino acids show elevated citrulline and ammonia; urinary orotic acid is ELEVATED. Which urea cycle enzyme is deficient?
21. A newborn diagnosed with phenylketonuria (PKU) due to phenylalanine hydroxylase deficiency is placed on a phenylalanine-restricted diet. In classic PKU, which metabolites accumulate and are responsible for the musty/mousy body odor?
22. Maple syrup urine disease (MSUD) is caused by deficiency of the branched-chain alpha-keto acid dehydrogenase complex. Which cofactor is required by this mitochondrial multienzyme complex, and which B-vitamin supplementation may partially rescue function in thiamine-responsive MSUD?
23. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency presents with Marfanoid habitus, ectopia lentis, thromboembolism, and intellectual disability. The lens dislocation in homocystinuria is characteristically in which direction, distinguishing it from Marfan syndrome?
24. A child with alkaptonuria will eventually develop ochronosis and arthritis. The enzyme deficient in this condition and the substrate that accumulates is:
25. A 2-year-old child with intellectual disability, fair skin, and a musty odor has plasma phenylalanine of 2000 μmol/L (normal <120). Phenylalanine hydroxylase activity is absent. What is the biochemical mechanism underlying the neurological damage in classic PKU?
26. Maple syrup urine disease (MSUD) results from deficiency of branched-chain alpha-keto acid dehydrogenase (BCKDH). Which cofactor deficiency would phenotypically mimic MSUD by secondarily impairing BCKDH function?
27. A neonate develops hyperammonemia, encephalopathy, and respiratory alkalosis within 48 hours of birth. Plasma amino acids show marked elevation of citrulline with very low argininosuccinate. Orotic acid in urine is elevated. What enzyme is deficient?
28. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is the most common inborn error of sulfur amino acid metabolism. Which metabolite supplementation can reduce plasma homocysteine in the pyridoxine-responsive form?
29. A neonate presents with lethargy, vomiting, hyperammonemia (NH3 1200 µmol/L), respiratory alkalosis, and plasma citrulline undetectable. Urine orotic acid is elevated. Which enzyme deficiency best explains this presentation?
30. A premature infant is found to have tyrosinemia type I. A 4-week course of NTBC (nitisinone) is initiated. NTBC inhibits which enzyme, and thereby prevents accumulation of which directly toxic metabolite?
31. Maple syrup urine disease (MSUD) results from deficiency of branched-chain α-keto acid dehydrogenase (BCKAD). This enzyme complex is analogous to pyruvate dehydrogenase and requires the same five cofactors. Which of the following cofactors is NOT required by BCKAD?
32. Classic homocystinuria due to cystathionine β-synthase (CBS) deficiency presents with ectopia lentis (downward), Marfanoid habitus, intellectual disability, and thromboembolism. Pyridoxine (B6) at high doses reduces homocysteine levels in responsive patients. What is the biochemical basis of this pyridoxine responsiveness?
33. A newborn is identified on tandem mass spectrometry screening with elevated C5-carnitine (isovalerylcarnitine). Urine organic acids show isovalerylglycine and 3-hydroxyisovalerate. This pattern is diagnostic of:
34. A newborn with undetected phenylketonuria (PKU) is breast-fed. By 3 months, the mother notices reduced alertness and poor feeding. Urinalysis shows phenylpyruvate. The enzyme deficiency most commonly responsible in classic PKU is:
35. In the urea cycle, N-acetylglutamate (NAG) is the essential allosteric activator of carbamoyl phosphate synthetase I (CPS-I). NAG synthesis increases after a protein-rich meal because:
36. Citrullinemia Type I (argininosuccinate synthetase deficiency) differs from ornithine transcarbamylase (OTC) deficiency in which key biochemical marker?
37. A patient with homocystinuria due to cystathionine beta-synthase (CBS) deficiency is also heterozygous for MTHFR C677T polymorphism. Treatment with pyridoxine (B6) is the first-line approach. The reason pyridoxine reduces homocysteine is:
38. Maple syrup urine disease (MSUD) results from deficiency of branched-chain alpha-keto acid dehydrogenase (BCKDH). Which three amino acids accumulate?
39. A 35-year-old woman presents with episodic severe abdominal pain, neuropsychiatric symptoms, and dark urine after taking sulfonamides. Urine porphobilinogen (PBG) is markedly elevated during attacks. The enzyme deficient in this condition and the pathway it normally catalyses is:
40. In classic maple syrup urine disease (MSUD), the enzymatic defect involves the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex. This complex requires multiple vitamins as cofactors. High-dose thiamine (vitamin B1) is therapeutically beneficial in some MSUD variants because thiamine pyrophosphate (TPP) is a cofactor for which component of BCKAD?
41. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency causes ectopia lentis, Marfanoid habitus, thromboembolism, and intellectual disability. In CBS deficiency, plasma homocysteine and methionine are elevated. High-dose pyridoxine treatment is effective in approximately 50% of patients because:
42. N-acetylglutamate (NAG) is an essential allosteric activator of which urea cycle enzyme, and what is the clinical significance of NAGS deficiency?
43. Citrullinaemia type I (ASS1 deficiency — argininosuccinate synthetase) causes hyperammonaemia. Why does hyperammonaemia impair brain function at the biochemical level?
44. Tetrahydrobiopterin (BH4) is a critical cofactor for phenylalanine hydroxylase (PAH). In BH4-deficient PKU (atypical PKU), which additional neurotransmitters are deficient, explaining the severe neurological phenotype?
45. A newborn screened positive for elevated phenylalanine has maternal PKU. The mother has PKU but the newborn's PAH gene is normal. What condition affects the newborn?
46. In ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder, which amino acid becomes conditionally essential and why?
47. A newborn is diagnosed with citrullinemia type I (deficiency of argininosuccinate synthetase in the urea cycle). Which metabolic consequences are expected?
48. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is pyridoxine-responsive in approximately 50% of cases. What is the biochemical rationale for this responsiveness?
49. MSUD (maple syrup urine disease) involves defective branched-chain alpha-keto acid dehydrogenase complex (BCKDH). Accumulation of which metabolites causes the characteristic neurotoxicity?
50. Maple syrup urine disease (MSUD) is caused by deficiency of branched-chain alpha-keto acid dehydrogenase complex (BCKAD). This enzyme requires which cofactor, also shared by pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase?
51. Homocysteine can be remethylated to methionine via two pathways. Which enzyme uses 5-methyltetrahydrofolate as the methyl donor and requires vitamin B12 as cofactor?
52. A 3-year-old boy presents with self-mutilating behaviour, hyperuricemia and neurological deficits. The enzyme deficient in Lesch-Nyhan syndrome is HGPRT, which catalyses which reaction?
53. ADA-SCID (adenosine deaminase deficiency) leads to T and B lymphocyte death. The accumulating toxic metabolite that primarily causes lymphocyte apoptosis is:
54. Orotic aciduria type 1 is caused by deficiency of UMP synthase (bifunctional enzyme). Which two enzymatic activities are absent, and what is the net metabolic consequence?
55. Allopurinol is used to treat gout. Its mechanism of action involves which biochemical step in purine catabolism?
56. In Lesch-Nyhan syndrome, the deficiency of HGPRT leads to accumulation of which substrate that is then degraded to uric acid, causing hyperuricemia and neurological features?
57. Adenosine deaminase (ADA) deficiency causes SCID predominantly affecting T lymphocytes. The toxic metabolite responsible for lymphocyte death is:
58. A patient with gout is started on allopurinol. The drug inhibits xanthine oxidase. Which intermediate accumulates in the blood and why does it cause fewer problems than uric acid?
59. Hereditary orotic aciduria (type I) is caused by deficiency of UMP synthase, a bifunctional enzyme. Which of the following does NOT occur in this condition?
60. A 3-year-old boy demonstrates self-mutilation, choreoathetosis, intellectual disability, and hyperuricaemia. Enzyme assay shows absent HGPRT activity. Which statement about the biochemical consequences is MOST accurate?
61. Allopurinol is used to treat gout. Beyond inhibiting xanthine oxidase, which additional biochemical effect contributes to its urate-lowering action?
62. Adenosine deaminase (ADA) deficiency causes SCID primarily because:
63. Orotic aciduria (type 1) presents with megaloblastic anaemia that does NOT respond to vitamin B12 or folate. The enzyme defect involves:
64. A 3-year-old boy presents with choreoathetosis, self-mutilation, hyperuricemia, and intellectual disability. Enzyme assay shows absent HGPRT (hypoxanthine-guanine phosphoribosyltransferase) activity. The mechanism by which HGPRT deficiency causes neurological dysfunction is best explained by:
65. A 4-year-old child has recurrent sinopulmonary infections, absent tonsils on examination, and profound lymphopenia affecting both T and B cells. Adenosine deaminase (ADA) enzyme activity is undetectable. The toxic metabolite responsible for lymphocyte death in ADA-SCID is:
66. Allopurinol is used in the treatment of gout and tumour lysis syndrome. In the biochemical treatment of Lesch-Nyhan syndrome, allopurinol effectively lowers uric acid but does NOT correct the neurological symptoms. This is because:
67. Orotic aciduria (type I hereditary) is characterised by megaloblastic anaemia, failure to thrive, and massive urinary orotic acid excretion. It is caused by deficiency of which bifunctional enzyme?
68. In Lesch-Nyhan syndrome, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency causes purine overproduction. The key mechanism linking HGPRT deficiency to increased de novo purine synthesis is:
69. A 4-year-old child with recurrent infections has profound lymphopenia affecting both T and B cells. Newborn screening showed elevated deoxyadenosine. The enzyme deficiency responsible and the mechanism of lymphocyte death is:
70. Allopurinol is used to prevent gout attacks. Its active metabolite oxypurinol inhibits xanthine oxidase as a suicide substrate. A patient on allopurinol who requires 6-mercaptopurine (6-MP) for leukemia will experience:
71. Orotic aciduria occurs in two distinct settings: UMP synthase deficiency (hereditary orotic aciduria) and treatment with allopurinol. The reason allopurinol causes orotic aciduria is:
72. In the purine salvage pathway, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the conversion of hypoxanthine + PRPP to IMP and guanine + PRPP to GMP. In Lesch-Nyhan syndrome (complete HGPRT deficiency), what biochemical consequence directly elevates uric acid?
73. Adenosine deaminase (ADA) deficiency causes SCID primarily through accumulation of which toxic metabolite in lymphocytes?
74. Allopurinol is used to lower uric acid in chronic tophaceous gout. Its active metabolite oxipurinol inhibits xanthine oxidase. As a result of enzyme inhibition, the immediate biochemical effect on xanthine and hypoxanthine levels is:
75. Orotic aciduria, presenting in infancy with megaloblastic anaemia unresponsive to B12 and folate, is caused by deficiency of which bifunctional enzyme of pyrimidine biosynthesis?
76. A 3-year-old boy has severe combined immunodeficiency (SCID), lymphopenia, and no B or T cells. Enzyme assay shows absent adenosine deaminase (ADA) activity. The toxic metabolite that accumulates and kills lymphocytes is:
77. Lesch-Nyhan syndrome results from HGPRT deficiency. The characteristic neurological finding that distinguishes it from simple gout is:
78. In de novo purine synthesis, the nitrogen atoms of the purine ring are derived from all of the following EXCEPT:
79. Allopurinol treats gout by inhibiting xanthine oxidase. A patient on allopurinol who also takes 6-mercaptopurine (6-MP) for leukaemia will have:
80. Orotic aciduria without hyperammonaemia is characteristic of deficiency of which enzyme?
81. A neonate presents with hyperammonaemia and orotic aciduria. Plasma citrulline is elevated. The most likely diagnosis is:
82. Maple syrup urine disease (MSUD) is caused by deficiency of branched-chain alpha-keto acid dehydrogenase (BCKAD) complex. Which cofactors are required for BCKAD function?
83. A 6-month-old presents with tyrosinaemia type I (fumarylacetoacetase deficiency). Succinylacetone is a diagnostic marker found in urine. It inhibits which enzyme, causing a secondary complication?
84. A neonate presents with hyperammonemia, seizures, and respiratory alkalosis. Plasma citrulline is markedly elevated. Urine orotic acid is elevated. Which urea cycle enzyme deficiency does this pattern indicate?
85. Tetrahydrobiopterin (BH4) is the cofactor for phenylalanine hydroxylase. BH4 deficiency can cause hyperphenylalaninemia indistinguishable from classic PKU on newborn screening. What additional neurological features distinguish BH4-deficient hyperphenylalaninemia from classic PKU?
86. Homocystinuria due to CBS (cystathionine beta-synthase) deficiency causes elevated plasma homocysteine and methionine. Which clinical feature is NOT typically seen in CBS-deficient homocystinuria?
87. A neonate with citrullinaemia type I (argininosuccinate synthetase deficiency) presents with hyperammonaemia. The treatment involves: (1) sodium benzoate + sodium phenylacetate and (2) arginine supplementation. The mechanism of arginine supplementation in this condition is:
88. Maple syrup urine disease (MSUD) is caused by deficiency of the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex. The neurological damage in MSUD is primarily due to:
89. Maple syrup urine disease (MSUD) presents in neonates with encephalopathy and sweet-smelling urine. The toxic accumulating metabolites are branched-chain alpha-keto acids from leucine, isoleucine, and valine. The primary neurotoxic mechanism is:
90. In the urea cycle, N-acetylglutamate (NAG) is an obligate allosteric activator of carbamoyl phosphate synthetase I (CPS-I). NAG synthase (NAGS) is activated by arginine. This regulatory circuit serves as a feed-forward signal because:
91. Maple syrup urine disease (MSUD) results from branched-chain alpha-keto acid dehydrogenase (BCKDH) complex deficiency. The toxic metabolites in MSUD cause cerebral edema and neurological deterioration primarily by:
92. A neonate develops progressive hyperammonemia, respiratory alkalosis, and encephalopathy. Plasma amino acid analysis shows elevated citrulline and elevated argininosuccinate. The enzyme defect is:
93. Tyrosinaemia type I (fumarylacetoacetase deficiency) produces succinylacetone, a potent inhibitor of delta-aminolevulinic acid dehydratase (ALAD). The resultant biochemical and clinical consequence is:
94. Hyperammonaemia in cirrhotics is managed with lactulose and rifaximin. At the molecular level, how does lactulose reduce blood ammonia?
95. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency causes elevated plasma homocysteine and methionine. Which pyridoxal phosphate (PLP)-dependent step is defective, and what is the rationale for pyridoxine treatment in CBS-responsive patients?
96. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is characterised by all of the following EXCEPT:
97. Maple syrup urine disease (MSUD) results from deficiency of branched-chain alpha-keto acid dehydrogenase (BCKAD). The toxic accumulating metabolites are:
98. A 3-year-old child with fair skin, eczema, and musty-smelling urine is brought for evaluation of intellectual disability and hyperactivity. Serum phenylalanine is 28 mg/dL (reference < 2 mg/dL). Which enzyme deficiency is responsible, and what is the direct metabolic consequence?
99. Transamination reactions are central to amino acid catabolism. Pyridoxal phosphate (PLP) is the essential cofactor for aminotransferases. In the alanine aminotransferase (ALT) reaction, alanine donates its amino group to alpha-ketoglutarate. What are the two products of this reaction?
100. A newborn screening panel detects elevated methionine in a 10-day-old infant. Further testing reveals homocysteine accumulation in blood and urine, lens dislocation, and skeletal abnormalities similar to Marfan syndrome. This condition is caused by deficiency of which enzyme in the methionine cycle?
101. During starvation, skeletal muscle releases alanine and glutamine as the major amino acids for interorgan nitrogen transport. Alanine reaches the liver where it undergoes transamination. The nitrogen eventually enters the urea cycle. Which two enzymes in the urea cycle are located in the mitochondrial matrix, while the remaining enzymes are cytosolic?
102. An 18-year-old male presents with progressive muscle weakness, cardiomyopathy, and peripheral neuropathy. Organic acid analysis of urine reveals elevated propionic acid and methylmalonic acid. Branched-chain amino acids such as valine, isoleucine, and threonine produce propionyl-CoA during catabolism. The accumulation pattern suggests a defect in which enzyme?