The PTS gene provides instructions for making an enzyme called 6-pyruvoyltetrahydropterin synthase. This enzyme is involved in the second of three steps in the production of a molecule called tetrahydrobiopterin (BH4). Other enzymes help 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 called neurotransmitters, which transmit signals between nerve cells in the brain. Because it helps enzymes carry out chemical reactions, tetrahydrobiopterin is known as a cofactor.
Health Conditions Related to Genetic Changes
More than 45 mutations in the PTS gene have been found to cause tetrahydrobiopterin deficiency. When this condition is caused by PTS gene mutations, it is known as 6-pyruvoyltetrahydropterin synthase (PTS) deficiency. PTS deficiency accounts for more than half of all cases of tetrahydrobiopterin deficiency.
Most PTS gene 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. Changes in 6-pyruvoyltetrahydropterin synthase greatly reduce or eliminate the enzyme's activity. 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 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 chemicals contribute to intellectual disability in people with PTS deficiency.More About This Health Condition
Other Names for This Gene
- 6-pyruvoyl-H4-pterin synthase
- 6-pyruvoyl-tetrahydropterin synthase
- PTP synthase
- sepiapterin synthase A
- sepiapterin synthesizing enzyme 1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
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- Thony B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Hum Mutat. 2006 Sep;27(9):870-8. doi: 10.1002/humu.20366. Citation on PubMed
- Wang L, Yu WM, He C, Chang M, Shen M, Zhou Z, Zhang Z, Shen S, Liu TT, Hsiao KJ. Long-term outcome and neuroradiological findings of 31 patients with 6-pyruvoyltetrahydropterin synthase deficiency. J Inherit Metab Dis. 2006 Feb;29(1):127-34. doi: 10.1007/s10545-006-0080-y. Citation on PubMed