What is the deficiency in classic PKU? What is the consequence of this deficiency?

What is the deficiency in classic PKU? What is the consequence of this deficiency?

• A. Phenylalanine hydroxylase; leads to phenylalanine buildup and tyrosine deficiency
• B. Tyrosine hydroxylase; leads to decreased phenylalanine
• C. Phenylalanine transaminase; no effect
• D. Homogentisate oxidase; increased phenylalanine

Answer: (A)

Classic PKU results from a deficiency of phenylalanine hydroxylase, the enzyme that normally converts phenylalanine to tyrosine with a required cofactor. When this enzyme isn’t functioning, phenylalanine cannot be properly metabolized and builds up in the blood and tissues. At the same time, the production of tyrosine falls because it isn’t being made from phenylalanine. This combination—phenylalanine accumulation and tyrosine deficiency—leads to neurotoxicity in the developing brain and reduced availability of tyrosine for making important compounds like melanin and catecholamines. That’s why the classic description is phenylalanine buildup with tyrosine deficiency. Other enzymes listed aren’t involved in the primary defect of classic PKU, and they wouldn’t produce the same pattern of findings.

Classic PKU results from a deficiency of phenylalanine hydroxylase, the enzyme that normally converts phenylalanine to tyrosine with a required cofactor. When this enzyme isn’t functioning, phenylalanine cannot be properly metabolized and builds up in the blood and tissues. At the same time, the production of tyrosine falls because it isn’t being made from phenylalanine. This combination—phenylalanine accumulation and tyrosine deficiency—leads to neurotoxicity in the developing brain and reduced availability of tyrosine for making important compounds like melanin and catecholamines. That’s why the classic description is phenylalanine buildup with tyrosine deficiency. Other enzymes listed aren’t involved in the primary defect of classic PKU, and they wouldn’t produce the same pattern of findings.