What is the biochemistry behind PKU?

Roberts and Martin. (1999) [6]

The lack of enzyme phenylalanine hydroxylase(PAH) causes PKU. Without this enzyme, a block is produced in the biochemical pathway. Normally, PAH converts phenylalanine to tyrosine. However in PKU patients, conversion of phenylalanine to tyrosine is unable to occur hence leading to accumulation of phenylalanine in the body. High levels of phenylalanine is known as hyperphenylalaninemia.

From the above diagram, tyrosine is used to produce thyroxine, dopa and subsequently melanin. However, in PKU the loss of enzyme causes shortage of all these products as well as tyrosine.

Increased phenylalanine levels in the blood leads to an increase in phenylpyruvic acid which is excreted in the urine of PKU patients. The detection of high phenylpyruvic acid  is useful in diagnosis to identify this disease.

Elmhurst College. (2003) [2]

Effects of the excess/absence of certain substances:

• The phenylpyruvic acid has also been shown to inhibit the enzyme pyruvate decarboxylase in brain. This leads to a decrease in energy for the developing brain and decreased myelinformation. Together, these could explain the mental retardation found in PKU. 

• Hyperphenylalaninemia results in congenital heart defects and microcephaly (An abnormally small head and brain). 

• The lack of melanin leads to decreased pigmentation of the person with PKU. Such patients therefore have blond hair and blue eyes and certain normally pigmented parts of the brain (such as the substantia nigra) may also lack pigment. 

• Lack of thyroxine may result in hypothyroidism. This can be treated with hormone replacement.

Roberts and Martin. (1999) [6]