ROSH Gastrointestinal Practice Exam

What is the most likely cause of phenylketonuria?

1. Conversion of phenylalanine to tyrosine

2. Conversion of tyrosine to phenylalanine

3. Deficiency of phenylalanine hydroxylase

4. Excess of phenylalanine hydroxylase

The correct answer is: Deficiency of phenylalanine hydroxylase

Phenylketonuria (PKU) is primarily caused by a deficiency of the enzyme phenylalanine hydroxylase. This enzyme is crucial for the metabolic pathway that converts phenylalanine, an amino acid found in many protein-containing foods, into tyrosine, another amino acid. When phenylalanine hydroxylase is deficient or nonfunctional, phenylalanine accumulates in the body and can lead to serious neurological consequences if not managed through dietary restrictions. Understanding this biochemical process underscores the importance of phenylalanine hydroxylase in maintaining amino acid balance within the body. Without this enzyme, phenylalanine cannot be effectively converted to tyrosine, and high levels of phenylalanine lead to the symptoms associated with PKU, including intellectual disability, developmental delays, and other neurological issues. The other options relate to aspects of the metabolic pathway but do not directly address the underlying cause of PKU. The conversion processes mentioned are contingent upon the presence and functionality of phenylalanine hydroxylase, further reinforcing why its deficiency is the critical issue in PKU.