PKU pathway block: A person with phenylketonuria cannot carry out which normal step in phenylalanine metabolism?

Introduction / Context:
Classical phenylketonuria (PKU) results from deficiency of phenylalanine hydroxylase or its cofactor tetrahydrobiopterin, blocking the hydroxylation of phenylalanine to tyrosine. Recognizing the precise blocked step is vital for understanding dietary therapy and the biochemical basis of newborn screening programs.

Given Data / Assumptions:

• Phenylalanine hydroxylase normally produces tyrosine from phenylalanine.
• In PKU, this conversion is impaired, elevating phenylalanine.
• Alternative metabolites (phenylpyruvate, phenyllactate, phenylacetate) accumulate.

Concept / Approach:
Identify the specific enzyme-catalyzed step that fails. The phenylalanine → tyrosine reaction is the first and key step of phenylalanine catabolism toward fumarate and acetoacetate. Other pairings in the options are not physiological conversions or refer to later steps not directly blocked by PAH deficiency.

Step-by-Step Solution:

Verification / Alternative check:
Elevated blood phenylalanine with low/normal tyrosine in newborn screening confirms the impaired phenylalanine → tyrosine step; dietary therapy reduces phenylalanine load and supplies tyrosine as a semiessential amino acid in PKU.

Why Other Options Are Wrong:

• Phenylalanine to isoleucine/lysine: not a metabolic conversion.
• Phenol into ketones: not relevant to amino acid catabolism.
• Tyrosine to fumarate: occurs downstream, not the defining PKU block.

Common Pitfalls:
Assuming PKU blocks later aromatic steps; the defect is at the very first hydroxylation reaction.

Final Answer:
Phenylalanine to tyrosine