Phenylalanine is an amino acid that must be obtained from the diet. It is needed to make tyrosine, an important substance from which the skin pigment melanin, the thyroid hormone thyroxine, and the neurotransmitters catecholamines are made. It is also degraded by conversion to 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 in another metabolic process.
Phenylketonuria
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 enzyme phenylalanine hydroxylase, which is responsible for converting phenylalanine to tyrosine. Phenylalanine therefore accumulates in the blood and tissues and damages the brain in particular.
If left untreated, this leads to delayed physical development, mental retardation and seizures. Since normal development is possible on a low-phenylalanine diet – beginning in the first two months of life – for more than 30 years, newborn screening has been conducted on the third to fifth day of life to determine whether there is evidence of phenylketonuria. The diet (fortified with special amino acids) should be followed at least until puberty as well as during pregnancy.
Alkaptonuria
In this case, the enzyme homogentisine oxigenase, which converts homogentisic acid into maleylacetoacetic acid, is absent. Therefore, homogentisic acid (in oxidized form as alkapton) is increasingly excreted in the urine as well as stored in various places in the body. This leads to:
- Joint changes and pain
- Calcification in tendons, ligaments and vessels
- Cardiac dysfunction
- Kidney stones
Incidentally, since this enzyme requires the assistance of vitamin C, its deficiency results in comparable complaints – as scurvy formerly widespread among sailors.
Tyrosinosis
This rare disease (frequency 1 : 100,000) lacks the enzyme fumaryl acetoacetase, which helps convert maleylacetoacetic acid. Instead, a toxic substance is produced from this. This damages the liver in particular, causing it to undergo connective tissue remodeling in infancy, which often leads to liver cancer later on. In addition, kidney function is also impaired.
For therapy, a drug is available that prevents toxic degradation products from being formed. In addition, a special diet that must be followed for the rest of the patient’s life is necessary.
