Question

Which of the following enzymes is deficient in a patient with Phenylketonuria if phenylalanine hydroxylase level is normal?

• A. Dihydrobiopterin reductase
• B. Phenylalanine hydroxylase
• C. Tyrosine aminotransferase
• D. Dihydropteridine reductase

Hint:

In cases of PKU with normal phenylalanine hydroxylase levels, dihydrobiopterin reductase deficiency can cause a similar metabolic disturbance.

Answer 1

The Correct Option is A

Phenylketonuria (PKU) is a metabolic disorder characterized by the inability to convert phenylalanine to tyrosine. This conversion is normally mediated by the enzyme phenylalanine hydroxylase. However, the normal function of this enzyme also requires the cofactor tetrahydrobiopterin (BH₄), which is regenerated from dihydrobiopterin (BH₂) by the enzyme dihydrobiopterin reductase.

In cases where phenylalanine hydroxylase is functioning normally, but PKU symptoms are present, the deficiency is likely in the enzyme responsible for regenerating BH₄. This enzyme is dihydrobiopterin reductase (also commonly referred to as dihydropteridine reductase in some sources). Without proper function of this enzyme, even if phenylalanine hydroxylase is present, the reaction cannot proceed efficiently due to the lack of available BH₄.

Therefore, in a patient with PKU and normal phenylalanine hydroxylase levels, dihydrobiopterin reductase deficiency is the cause.