PTS

The PTS gene provides instructions for making an enzyme called 6-pyruvoyltetrahydropterin synthase. This enzyme is responsible for the second of three steps in the production of a molecule called tetrahydrobiopterin (BH4). Other enzymes carry out the first and third steps in this process.

Tetrahydrobiopterin plays a critical role in processing several protein building blocks (amino acids) in the body. For example, it works with the enzyme phenylalanine hydroxylase to convert an amino acid called phenylalanine into another amino acid, tyrosine. Tetrahydrobiopterin is also involved in reactions that produce chemicals in the brain called neurotransmitters, which transmit signals between nerve cells. Because it helps enzymes carry out chemical reactions, tetrahydrobiopterin is known as a cofactor.

tetrahydrobiopterin deficiency - caused by mutations in the PTS gene

Mutations in the PTS gene are the most common cause of tetrahydrobiopterin deficiency. When PTS mutations underlie this disorder, it is known as 6-pyruvoyltetrahydropterin synthase (PTS) deficiency. More than 40 disease-causing mutations have been identified in the PTS gene. Most of these mutations change single amino acids in 6-pyruvoyltetrahydropterin synthase, although some mutations insert or delete small amounts of DNA in the PTS gene or disrupt the way the gene's instructions are used to make the enzyme.

Mutations in the PTS gene greatly reduce or eliminate the activity of 6-pyruvoyltetrahydropterin synthase. Without enough of this enzyme, little or no tetrahydrobiopterin is produced. As a result, this cofactor is not available to participate in chemical reactions such as the conversion of phenylalanine to tyrosine. If phenylalanine from the diet is not converted to tyrosine, it can build up to toxic levels in the blood and other tissues. Nerve cells in the brain are particularly sensitive to phenylalanine levels, which is why excessive amounts of this substance can cause brain damage.

Additionally, a reduction in 6-pyruvoyltetrahydropterin synthase activity disrupts the production of certain neurotransmitters in the brain. Because neurotransmitters are necessary for normal brain function, changes in the levels of these brain chemicals contribute to mental impairment in people with tetrahydrobiopterin deficiency.