Brain damage in phenylketonuria is due to accumulation of ?
**Core Concept**
Phenylketonuria (PKU) is a genetic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH), leading to the accumulation of phenylalanine (Phe) in the body. This accumulation is toxic to the developing brain, resulting in intellectual disability and other neurological problems.
**Why the Correct Answer is Right**
The accumulation of phenylalanine in PKU is due to the impaired conversion of phenylalanine to tyrosine, which is catalyzed by the enzyme phenylalanine hydroxylase. Normally, PAH converts Phe to tyrosine, which is then used in the synthesis of neurotransmitters and other important molecules. In PKU, the defective PAH enzyme leads to the accumulation of Phe, causing damage to the brain and other organs.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because the accumulation of tryptophan is not directly related to PKU. While tryptophan is an amino acid, PKU is specifically caused by the accumulation of phenylalanine.
**Option B:** This option is incorrect because the accumulation of tyrosine is actually the desired outcome of the PAH enzyme's action. In PKU, tyrosine levels are normal or low because the enzyme is defective.
**Option C:** This option is incorrect because the accumulation of aspartate is not directly related to PKU. Aspartate is an amino acid that is not directly involved in the PAH enzyme reaction.
**Clinical Pearl / High-Yield Fact**
PKU is a classic example of a genetic disorder that can be managed with dietary restriction. A strict diet low in phenylalanine can prevent the accumulation of this toxic amino acid and prevent brain damage.
**Correct Answer: D. Phenylalanine.**