The catabolism of phenylalanine is a vital biochemical pathway for B.Pharm students to master, linking amino acid metabolism, enzyme mechanisms, cofactor biochemistry and inborn errors like phenylketonuria (PKU). Phenylalanine is primarily converted to tyrosine by phenylalanine hydroxylase (PAH) with tetrahydrobiopterin (BH4) as cofactor; alternative transamination forms phenylpyruvate and downstream phenylacetate. Downstream tyrosine degradation yields fumarate and acetoacetate via enzymes such as 4-hydroxyphenylpyruvate dioxygenase and fumarylacetoacetase; defects cause disorders like alkaptonuria and tyrosinemia. It covers enzyme kinetics, BH4 regeneration, transamination side pathways, diagnostic biochemical markers (plasma phenylalanine, phenylketones by tandem MS) and clinical management including dietary restriction and sapropterin therapy. These MCQs emphasize clinical correlations, lab markers and treatment principles. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which enzyme catalyzes the primary conversion of phenylalanine to tyrosine?
- Phenylalanine hydroxylase
- Aromatic L-amino acid decarboxylase
- Phenylpyruvate transaminase
- Tyrosine aminotransferase
Correct Answer: Phenylalanine hydroxylase
Q2. Which cofactor is essential for phenylalanine hydroxylase activity?
- Tetrahydrobiopterin (BH4)
- Pyridoxal phosphate (PLP)
- Thiamine pyrophosphate (TPP)
- Nicotinamide adenine dinucleotide (NAD+)
Correct Answer: Tetrahydrobiopterin (BH4)
Q3. A deficiency of dihydropteridine reductase primarily impairs regeneration of which molecule?
- Tetrahydrobiopterin (BH4)
- Pyridoxal phosphate (PLP)
- Biotin
- FADH2
Correct Answer: Tetrahydrobiopterin (BH4)
Q4. Classical phenylketonuria (PKU) is most commonly caused by mutations in the gene encoding:
- Phenylalanine hydroxylase (PAH)
- Tyrosine aminotransferase (TAT)
- Homogentisate oxidase (HGD)
- Fumarylacetoacetase (FAH)
Correct Answer: Phenylalanine hydroxylase (PAH)
Q5. Which diagnostic marker is most directly elevated in untreated PKU?
- Plasma phenylalanine
- Plasma tyrosine
- Plasma homogentisic acid
- Plasma fumarate
Correct Answer: Plasma phenylalanine
Q6. Alternative transamination of phenylalanine yields which keto-acid?
- Phenylpyruvate
- 4-Hydroxyphenylpyruvate
- Fumarylacetoacetate
- Phenylacetylglutamine
Correct Answer: Phenylpyruvate
Q7. Which therapy is a synthetic form of BH4 used in some PKU patients?
- Sapropterin
- Levocarnitine
- S-adenosylmethionine
- Allopurinol
Correct Answer: Sapropterin
Q8. The Guthrie test historically detected PKU via bacterial growth inhibition in presence of:
- β-2-thienylalanine
- p-Aminobenzoic acid
- Galactose
- Hydroxocobalamin
Correct Answer: β-2-thienylalanine
Q9. Which enzyme deficiency leads to accumulation of homogentisic acid and alkaptonuria?
- Homogentisate oxidase
- 4-Hydroxyphenylpyruvate dioxygenase
- Fumarylacetoacetase
- Phenylalanine hydroxylase
Correct Answer: Homogentisate oxidase
Q10. Tyrosine produced from phenylalanine is a precursor for which of the following molecules?
- Catecholamines and melanin
- Vitamin B12 and heme
- Thyroid hormone exclusively
- Glutathione and creatine
Correct Answer: Catecholamines and melanin
Q11. Which vitamin-derived cofactor is required for transamination reactions often involved in amino acid catabolism?
- Pyridoxal phosphate (PLP)
- Riboflavin (FAD)
- Niacin (NAD+)
- Biotin
Correct Answer: Pyridoxal phosphate (PLP)
Q12. Elevated levels of phenylacetate and phenylpropionate in urine are associated with:
- Untreated phenylketonuria (PKU)
- Homocystinuria
- Alkaptonuria
- Maple syrup urine disease
Correct Answer: Untreated phenylketonuria (PKU)
Q13. Which newborn screening technique is now commonly used to quantify phenylalanine levels?
- Tandem mass spectrometry (MS/MS)
- Western blotting
- ELISA for PAH protein
- Urine dipstick
Correct Answer: Tandem mass spectrometry (MS/MS)
Q14. BH4-responsive hyperphenylalaninemia indicates residual activity of which enzyme?
- Phenylalanine hydroxylase
- Homogentisate oxidase
- 4-Hydroxyphenylpyruvate dioxygenase
- Tyrosine hydroxylase
Correct Answer: Phenylalanine hydroxylase
Q15. What is the inheritance pattern of classic PAH-related PKU?
- Autosomal recessive
- Autosomal dominant
- X-linked recessive
- Mitochondrial
Correct Answer: Autosomal recessive
Q16. Which clinical feature is commonly associated with untreated PKU in infants?
- Intellectual disability and seizures
- Jaundice
- Muscle hypertrophy
- Hypoglycemia only
Correct Answer: Intellectual disability and seizures
Q17. Maternal PKU can cause which fetal complications if maternal phenylalanine is uncontrolled?
- Microcephaly and congenital heart defects
- Polydactyly
- Sickle cell disease
- Hirschsprung disease
Correct Answer: Microcephaly and congenital heart defects
Q18. Which enzyme acts on 4-hydroxyphenylpyruvate in tyrosine catabolism?
- 4-Hydroxyphenylpyruvate dioxygenase (HPPD)
- Homogentisate oxidase
- Fumarylacetoacetase
- Phenylalanine hydroxylase
Correct Answer: 4-Hydroxyphenylpyruvate dioxygenase (HPPD)
Q19. Deficiency of fumarylacetoacetase causes which metabolic disease?
- Tyrosinemia type I
- Alkaptonuria
- PKU variant
- Homocystinuria
Correct Answer: Tyrosinemia type I
Q20. Which accumulated metabolite is characteristic of tyrosinemia type I?
- Succinylacetone
- Homogentisic acid
- Phenylpyruvate
- Phenylacetate
Correct Answer: Succinylacetone
Q21. Which therapeutic agent inhibits 4-hydroxyphenylpyruvate dioxygenase and is used in hereditary tyrosinemia type I management?
- NTBC (nitisinone)
- Sapropterin
- Allopurinol
- Penicillamine
Correct Answer: NTBC (nitisinone)
Q22. PEG-PAL (pegylated phenylalanine ammonia lyase) is designed to:
- Degrade circulating phenylalanine enzymatically
- Enhance PAH gene expression
- Block BH4 synthesis
- Increase tyrosine hydroxylase activity
Correct Answer: Degrade circulating phenylalanine enzymatically
Q23. Large neutral amino acid (LNAA) supplementation in PKU therapy primarily works by:
- Competing with phenylalanine for transport across the blood-brain barrier
- Increasing renal excretion of phenylalanine
- Activating PAH allosterically
- Inhibiting intestinal absorption of phenylalanine
Correct Answer: Competing with phenylalanine for transport across the blood-brain barrier
Q24. Which laboratory ratio is useful in newborn screening to distinguish PKU from transient hyperphenylalaninemia?
- Phenylalanine/tyrosine ratio
- Tyrosine/phenylalanine ratio
- Methionine/cysteine ratio
- Leucine/isoleucine ratio
Correct Answer: Phenylalanine/tyrosine ratio
Q25. BH4 is synthesized de novo from which precursor molecule class?
- GTP-derived pteridine pathway
- Amino acid sulfur metabolism
- Lipid-derived isoprenoids
- Carbohydrate pentose pathway
Correct Answer: GTP-derived pteridine pathway
Q26. Which enzyme deficiency causes elevated urinary 4-hydroxyphenylpyruvate and tyrosine levels but not classic alkaptonuria?
- 4-Hydroxyphenylpyruvate dioxygenase deficiency
- Phenylalanine hydroxylase deficiency
- Fumarylacetoacetase deficiency
- Homogentisate oxidase deficiency
Correct Answer: 4-Hydroxyphenylpyruvate dioxygenase deficiency
Q27. In BH4 deficiency, besides hyperphenylalaninemia, patients may also have deficiency in synthesis of which neurotransmitters?
- Dopamine and serotonin
- GABA and glycine
- Acetylcholine and histamine
- Epinephrine exclusively
Correct Answer: Dopamine and serotonin
Q28. The biochemical basis for cognitive impairment in PKU is mainly due to:
- Toxic effects of elevated brain phenylalanine and reduced tyrosine-derived neurotransmitters
- Defective myelin synthesis from lack of methionine
- Accumulation of homogentisic acid in the brain
- Hypoglycemia from amino acid catabolism
Correct Answer: Toxic effects of elevated brain phenylalanine and reduced tyrosine-derived neurotransmitters
Q29. Which diagnostic assay directly measures PAH enzyme activity in cultured cells?
- PAH activity assay using radiolabeled phenylalanine
- ELISA for phenylalanine
- Urine ketone strip test
- Hemoglobin electrophoresis
Correct Answer: PAH activity assay using radiolabeled phenylalanine
Q30. What is the primary clinical rationale for supplementing tyrosine in PKU diets?
- Tyrosine becomes an essential amino acid when phenylalanine conversion is impaired
- Tyrosine directly lowers plasma phenylalanine by binding it
- Tyrosine cures PAH gene mutations
- Tyrosine increases BH4 synthesis
Correct Answer: Tyrosine becomes an essential amino acid when phenylalanine conversion is impaired
Q31. Which organ is the major site of phenylalanine catabolism?
- Liver
- Kidney
- Brain
- Skeletal muscle
Correct Answer: Liver
Q32. Which metabolite is produced by gut bacteria from excess phenylalanine and may contribute to odor in PKU?
- Phenylacetate
- Tyrosol
- Urobilinogen
- Indican
Correct Answer: Phenylacetate
Q33. In phenylalanine catabolism, conversion of phenylalanine to phenylpyruvate involves which enzyme type?
- Aminotransferase (transaminase)
- Hydroxylase
- Monooxygenase
- Carboxylase
Correct Answer: Aminotransferase (transaminase)
Q34. A high phenylalanine/tyrosine ratio in newborn screening suggests:
- Impaired conversion of phenylalanine to tyrosine
- Excess tyrosine intake
- Fasting artifact only
- Vitamin C deficiency
Correct Answer: Impaired conversion of phenylalanine to tyrosine
Q35. Which molecular therapy approach aims to correct PAH mutations at DNA level?
- Gene therapy delivering functional PAH gene
- BH4 supplementation
- Dietary phenylalanine restriction
- Enzyme replacement with PEG-PAL only
Correct Answer: Gene therapy delivering functional PAH gene
Q36. Which biochemical consequence is expected when BH4 levels are low?
- Reduced PAH activity and increased plasma phenylalanine
- Increased PLP-dependent transamination
- Enhanced tyrosine degradation to fumarate
- Decreased phenylacetate excretion only
Correct Answer: Reduced PAH activity and increased plasma phenylalanine
Q37. Heterozygous carriers of PAH mutations typically exhibit which phenotype?
- Usually asymptomatic with normal phenylalanine metabolism
- Classical PKU phenotype
- Severe intellectual disability
- Alkaptonuria features
Correct Answer: Usually asymptomatic with normal phenylalanine metabolism
Q38. An elevated urinary phenylketone in PKU indicates accumulation of which compound?
- Phenylpyruvate
- Homogentisic acid
- Succinylacetone
- Phenylalanine hydroxylase
Correct Answer: Phenylpyruvate
Q39. Which of the following is NOT a downstream product of tyrosine catabolism?
- Phenylacetate
- Fumarate
- Acetoacetate
- Homogentisic acid
Correct Answer: Phenylacetate
Q40. Which enzyme converts tyrosine to p-hydroxyphenylpyruvate?
- Tyrosine aminotransferase
- Tyrosine hydroxylase
- Phenylalanine hydroxylase
- Homogentisate oxidase
Correct Answer: Tyrosine aminotransferase
Q41. Which metabolic product causes the darkening of urine on standing in alkaptonuria?
- Homogentisic acid
- Phenylpyruvate
- Succinylacetone
- Phenylacetylglutamine
Correct Answer: Homogentisic acid
Q42. Which test provides a quantitative measurement of plasma phenylalanine concentration in a clinical lab?
- Liquid chromatography–tandem mass spectrometry (LC-MS/MS)
- Urine dipstick
- Complete blood count
- Serum electrolyte panel
Correct Answer: Liquid chromatography–tandem mass spectrometry (LC-MS/MS)
Q43. Which enzyme defect is directly targeted by nitisinone (NTBC) therapy?
- 4-Hydroxyphenylpyruvate dioxygenase
- Fumarylacetoacetase
- Phenylalanine hydroxylase
- Homogentisate oxidase
Correct Answer: 4-Hydroxyphenylpyruvate dioxygenase
Q44. Which amino acid becomes conditionally essential in PAH deficiency?
- Tyrosine
- Methionine
- Tryptophan
- Leucine
Correct Answer: Tyrosine
Q45. Plasma phenylalanine levels above which approximate concentration typically indicate classical PKU (untreated)?
- >1200 µmol/L
- 50–100 µmol/L
- 200–400 µmol/L
- <100 µmol/L
Correct Answer: >1200 µmol/L
Q46. Which molecular diagnostic method is commonly used to identify PAH gene mutations?
- DNA sequencing of the PAH gene
- Western blot for PAH protein
- Urinalysis for phenylketones
- Chromosomal karyotyping
Correct Answer: DNA sequencing of the PAH gene
Q47. Which pharmacologic strategy reduces cerebral phenylalanine toxicity by altering blood-brain transport?
- Supplementation with large neutral amino acids (LNAA)
- High-dose vitamin C
- Iron chelation therapy
- Steroid administration
Correct Answer: Supplementation with large neutral amino acids (LNAA)
Q48. Which clinical measurement is most important to monitor in children under dietary therapy for PKU?
- Regular plasma phenylalanine concentrations
- Serum sodium
- Urine albumin
- Fasting glucose
Correct Answer: Regular plasma phenylalanine concentrations
Q49. Enzymatic degradation of phenylalanine to trans-cinnamic acid is catalyzed by which therapeutic enzyme used experimentally?
- Phenylalanine ammonia lyase (PAL)
- Monoamine oxidase
- Urocanase
- Phenylalanine decarboxylase
Correct Answer: Phenylalanine ammonia lyase (PAL)
Q50. Which statement best summarizes the clinical importance of understanding phenylalanine catabolism for B.Pharm students?
- It links biochemical pathways to diagnostic methods, genetic counseling and pharmacological management of disorders like PKU and tyrosinemia
- It only concerns dietary recommendations with no drug implications
- It is relevant only for basic science researchers and not pharmacists
- It focuses solely on liver anatomy without clinical application
Correct Answer: It links biochemical pathways to diagnostic methods, genetic counseling and pharmacological management of disorders like PKU and tyrosinemia
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