Q.1 Deficiency of the enzyme phenylalanine hydroxylase causes Phenylketonuria. Phenylalanine
hydroxylase converts phenylalanine to
(A) tryptophan (B) alanine (C) tyrosine (D) threonine
Phenylalanine hydroxylase converts phenylalanine to tyrosine, making option (C) the correct answer. Deficiency of this enzyme leads to phenylketonuria (PKU), a genetic disorder where phenylalanine accumulates, causing severe health issues if untreated. Understanding the metabolic pathway and options clarifies why this reaction is critical for CSIR NET Life Sciences preparation.
Question Breakdown
Phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of phenylalanine using tetrahydrobiopterin (BH4) and molecular oxygen, inserting a hydroxyl group at the para position of the phenyl ring. This irreversible reaction is the primary catabolic step for phenylalanine in the liver, preventing toxic buildup. Without PAH activity, phenylalanine levels rise, leading to PKU symptoms like intellectual disability.
Option Analysis
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(A) Tryptophan: Incorrect, as tryptophan is hydroxylated by a separate enzyme, tryptophan hydroxylase, to 5-hydroxytryptophan, not involving phenylalanine.
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(B) Alanine: Incorrect; alanine arises from pyruvate via transamination, unrelated to phenylalanine metabolism.
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(C) Tyrosine: Correct; PAH directly converts phenylalanine to tyrosine, a key step confirmed across biochemical pathways.
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(D) Threonine: Incorrect; threonine is an essential amino acid from dietary sources, degraded via separate pathways like serine synthesis, not linked to PAH.
Phenylalanine hydroxylase deficiency causes phenylketonuria (PKU), a metabolic disorder where the enzyme fails to convert phenylalanine to tyrosine, leading to toxic accumulation. This autosomal recessive condition affects 1 in 10,000-15,000 newborns and requires early newborn screening for management. For CSIR NET aspirants, mastering this pathway is essential for biochemistry and genetics sections.
Biochemical Reaction
PAH, a hepatic enzyme, hydroxylates L-phenylalanine to L-tyrosine using BH4 as a cofactor and O2, producing dihydrobiopterin (recycled by dihydrobiopterin reductase). The reaction is:
L-Phenylalanine+O2+BH4→L-Tyrosine+H2O+BH2 Tyrosine then feeds into catecholamine synthesis or further catabolism.
PKU Pathophysiology
In PKU, PAH mutations (over 500 identified) reduce enzyme activity, elevating blood phenylalanine above 20 mg/dL, which crosses the blood-brain barrier and impairs myelination and neurotransmission. Untreated cases cause microcephaly, seizures, and IQ below 50; maternal PKU risks fetal defects.
Clinical Management
Treatment involves lifelong low-phenylalanine diet (supplemented formula), sapropterin (BH4 analog) for responsive cases, and pegvaliase for adults. Monitoring targets phenylalanine at 2-6 mg/dL in children.
Exam Relevance
For competitive exams like CSIR NET, questions test this direct conversion, distinguishing distractors like tryptophan (tryptophan hydroxylase substrate). Key fact: Phenylalanine is essential; tyrosine becomes conditionally essential in PKU.
