Phenylketonuria PKU Cause - CSIR NET LIFE SCIENCE COACHING | NTA NET LIFE SCIENCE

Q65.Phenylketonuria is caused by dysfunction of

(1) Phenylalanine hydroxylase
(2) Phenylalanine monooxygenase
(3) Phenylalanine mutase
(4) Phenylalanine dioxygenase

Phenylketonuria Enzyme Deficiency Explained

Phenylketonuria (PKU) results from deficiency in phenylalanine hydroxylase, causing toxic phenylalanine buildup in blood and tissues.

Option (1) Phenylalanine hydroxylase causes PKU due to PAH gene mutations impairing Phe-to-Tyr conversion.

This autosomal recessive disorder leads to intellectual disability if untreated, preventable via low-Phe diet and newborn screening.

Option	Enzyme	Explanation
(1) Phenylalanine hydroxylase	Correct	PAH converts phenylalanine to tyrosine using BH4 cofactor; deficiency causes Phe accumulation and phenylketones in urine.
(2) Phenylalanine monooxygenase	Incorrect	Not a standard enzyme; monooxygenases handle other substrates like tryptophan, unrelated to PKU pathway.
(3) Phenylalanine mutase	Incorrect	No such enzyme exists in phenylalanine metabolism; mutases rearrange carbons (e.g., methylmalonyl), not relevant here.
(4) Phenylalanine dioxygenase	Incorrect	Dioxygenases act on other amino acids (e.g., prolyl hydroxylase); PKU specifically involves monooxygenation by PAH.

PAH catalyzes L-phenylalanine + O₂ + tetrahydrobiopterin → L-tyrosine + dihydrobiopterin + H₂O in liver.

Without functional PAH, Phe converts to phenylpyruvate/lactate, detected in urine, explaining “phenylketonuria” name.

Tetrahydrobiopterin (BH4) cofactor defects cause rare PKU variants (~2%), treated differently.