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?

• A Pyridoxal phosphate (PLP)
• B Flavin adenine dinucleotide (FAD)
• C Methylcobalamin
• D Tetrahydrobiopterin (BH4) ✓

Explanation

Phenylalanine hydroxylase requires tetrahydrobiopterin (BH4) as an essential cofactor for the hydroxylation of phenylalanine to tyrosine. Defects in BH4 synthesis or regeneration (by dihydropteridine reductase) cause a malignant form of hyperphenylalaninemia because BH4 is also required for tyrosine hydroxylase and tryptophan hydroxylase, impairing synthesis of dopamine, norepinephrine, epinephrine, and serotonin. This variant does not respond to dietary phenylalanine restriction alone.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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