Question:medium
A patient has high phenylalanine levels despite normal phenylalanine hydroxylase. Which cofactor deficiency is most likely responsible?
A patient has high phenylalanine levels despite normal phenylalanine hydroxylase. Which cofactor deficiency is most likely responsible?
Show Hint
Phenylalanine hydroxylase requires BH4. BH4 deficiency can mimic phenylketonuria.
Updated On: May 14, 2026
- Tetrahydrofolate
- Tetrahydrobiopterin (BH4)
- Thiamine
- Pyridoxine
Show Solution
The Correct Option is B
Solution and Explanation
Step 1: Understanding the Question:
Phenylketonuria (PKU) is typically caused by a deficiency of the enzyme Phenylalanine Hydroxylase (PAH).
However, if the enzyme itself is normal but phenylalanine levels are high, the defect must lie in the essential cofactor required by that enzyme.
Step 2: Detailed Explanation:
The PAH Reaction: Phenylalanine Hydroxylase converts Phenylalanine into Tyrosine. For this reaction to occur, it requires the cofactor Tetrahydrobiopterin (BH4) and molecular oxygen.
Atypical (Malignant) PKU: This condition occurs when BH4 is deficient, either due to a defect in its synthesis or a defect in its recycling enzyme (Dihydropteridine reductase).
Multi-pathway Impact: BH4 is not just for phenylalanine. It is also the necessary cofactor for Tyrosine Hydroxylase (to make Dopamine/Epinephrine) and Tryptophan Hydroxylase (to make Serotonin).
Clinical Severity: Because BH4 deficiency affects neurotransmitter production in addition to causing hyperphenylalaninemia, these patients suffer from severe neurological deterioration even if they follow a low-phenylalanine diet.
Differentiating Option A: Tetrahydrofolate (THF) is involved in 1-carbon metabolism but is not the cofactor for phenylalanine hydroxylase.
Step 3: Final Answer:
The mandatory cofactor for the conversion of phenylalanine to tyrosine is Tetrahydrobiopterin (BH4); its deficiency causes atypical PKU.
Phenylketonuria (PKU) is typically caused by a deficiency of the enzyme Phenylalanine Hydroxylase (PAH).
However, if the enzyme itself is normal but phenylalanine levels are high, the defect must lie in the essential cofactor required by that enzyme.
Step 2: Detailed Explanation:
The PAH Reaction: Phenylalanine Hydroxylase converts Phenylalanine into Tyrosine. For this reaction to occur, it requires the cofactor Tetrahydrobiopterin (BH4) and molecular oxygen.
Atypical (Malignant) PKU: This condition occurs when BH4 is deficient, either due to a defect in its synthesis or a defect in its recycling enzyme (Dihydropteridine reductase).
Multi-pathway Impact: BH4 is not just for phenylalanine. It is also the necessary cofactor for Tyrosine Hydroxylase (to make Dopamine/Epinephrine) and Tryptophan Hydroxylase (to make Serotonin).
Clinical Severity: Because BH4 deficiency affects neurotransmitter production in addition to causing hyperphenylalaninemia, these patients suffer from severe neurological deterioration even if they follow a low-phenylalanine diet.
Differentiating Option A: Tetrahydrofolate (THF) is involved in 1-carbon metabolism but is not the cofactor for phenylalanine hydroxylase.
Step 3: Final Answer:
The mandatory cofactor for the conversion of phenylalanine to tyrosine is Tetrahydrobiopterin (BH4); its deficiency causes atypical PKU.
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