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?
- A Tetrahydrobiopterin (BH4) ✓
- B Pyridoxal phosphate (PLP)
- C Flavin adenine dinucleotide (FAD)
- D Molybdenum cofactor
Explanation
Tetrahydrobiopterin (BH4) is the essential cofactor for all three aromatic amino acid hydroxylases: phenylalanine hydroxylase (PAH), tyrosine hydroxylase (rate-limiting for catecholamine synthesis), and tryptophan hydroxylase (rate-limiting for serotonin synthesis). BH4 deficiency causes malignant hyperphenylalaninemia, which does not respond to phenylalanine restriction alone and requires BH4 supplementation. The identification of BH4 deficiency is critical because neurotransmitter deficiency (dopamine, serotonin) contributes to the neurological deterioration beyond what PAH deficiency alone would cause.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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