PKU and dietary load: In a person with phenylketonuria who consumes foods high in phenylalanine, which metabolite would most characteristically accumulate?

Introduction / Context:
Dietary management of phenylketonuria (PKU) aims to prevent accumulation of phenylalanine and its toxic derivatives. When intake exceeds metabolic capacity due to phenylalanine hydroxylase deficiency, alternative catabolic routes dominate, producing characteristic metabolites that can be measured clinically and that contribute to neuropathology if levels remain high.

Given Data / Assumptions:

• Classical PKU blocks phenylalanine → tyrosine conversion.
• Transamination of excess phenylalanine forms phenylpyruvate.
• Phenylpyruvate can be further reduced to phenyllactate or converted to phenylacetate.

Concept / Approach:
Under a high-phenylalanine load, the first and most proximate abnormal product is phenylpyruvate. Although phenylalanine itself also rises, the question asks for the metabolite that characteristically accumulates downstream in PKU. Urinary phenylketones (phenylpyruvate, phenylacetate, phenyllactate) give the disorder its name and are detectable in screening tests.

Step-by-Step Solution:

Verification / Alternative check:
Biochemical profiling in untreated PKU shows elevated plasma phenylalanine and increased urinary phenylpyruvate; dietary restriction reduces these levels and prevents neurocognitive impairment.

Why Other Options Are Wrong:

• Tyrosine tends to be low or normal in classical PKU.
• Isoleucine is unrelated to phenylalanine catabolism.
• Phenylacetate may rise but is downstream; phenylpyruvate is the immediate, signature keto-acid.

Common Pitfalls:
Answering with phenylalanine itself; while elevated, the question focuses on the characteristic metabolite produced by the aberrant pathway.

Final Answer:
Phenylpyruvate