Disorders of phenylalanine-tyrosine metabolism

Disorders of phenylalanine-tyrosine metabolism

Phenylalanine is an amino acid that must be consumed through food. It is needed to produce tyrosine, an essential substance from which the skin pigment melanin, the thyroid hormone thyroxine and the messenger substances catecholamines are produced. It is also broken down by conversion into homogentisic acid.

The normal phenylalanine-tyrosine metabolic pathway is as follows: phenylalanine > tyrosine > homogentisic acid > maleylacetoacetic acid > acetoacetic acid/fumaric acid. The last two substances are then further converted into another metabolic process.


PKU is the most common congenital disorder of amino acid metabolism (1 in 7,000 to 10,000 newborns). There are currently an estimated 2,500 PKU sufferers in Germany. There is a defect in the phenylalanine hydroxylase, responsible for converting phenylalanine to tyrosine. This is why phenylalanine accumulates in the blood and tissues and damages the brain.

If left untreated, this leads to delayed physical development, mental retardation and seizures. Since normal development is possible with a diet low in phenylalanine, starting in the first two months of life, newborn screening on the third to fifth day of life has been carried out for over 30 years to check whether there is evidence of phenylketonuria. The diet (enriched with particular amino acids) should be followed until puberty and during pregnancy.



The enzyme homogentisinoxygenase, which converts homogentisic acid into maleylacetoacetic acid, is missing here. Therefore, homogentisic acid (in oxidized form as alkapton) is increasingly excreted in the urine and stored in various places in the body. This leads to:

  • Joint changes and pain
  • Limescale deposits in tendons, ligaments and vessels
  • Cardiac dysfunction
  • kidney stones

By the way, Since this enzyme requires the help of vitamin C, a lack of it can cause similar symptoms – as scurvy was previously widespread among sailors.


This rare disease (frequency 1:100,000) lacks the enzyme fumaryl acetoacetate, which helps convert maleyl acetoacetic acid. Instead, a toxic substance is produced from this. This damages the liver in particular so that it is converted into connective tissue in infancy, which often later develops into liver cancer. In addition, kidney function is also impaired.

A medication is available for therapy that prevents toxic degradation products from being formed. In addition, a special diet that must be maintained throughout life is necessary.



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