6-pyruvoyltetrahydropterin synthase

6-Pyruvoyltetrahydropterin synthase (PTS) is an enzyme that in humans is encoded by the PTS gene. This enzyme plays a crucial role in the biosynthesis of tetrahydrobiopterin (BH4), which is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases. These hydroxylases are necessary for the synthesis of neurotransmitters such as serotonin, melatonin, dopamine, and norepinephrine. Additionally, BH4 is involved in the production of nitric oxide (NO) by nitric oxide synthase.

Function

6-Pyruvoyltetrahydropterin synthase catalyzes the conversion of 7,8-dihydroneopterin triphosphate to 6-pyruvoyl-tetrahydropterin, which is a critical step in the biosynthetic pathway leading to the formation of tetrahydrobiopterin. The activity of PTS is vital for maintaining sufficient levels of BH4 in the body. Without adequate BH4, the hydroxylation of the aforementioned amino acids is compromised, leading to a reduction in the synthesis of key neurotransmitters and nitric oxide.

Clinical Significance

Mutations in the PTS gene can lead to 6-pyruvoyltetrahydropterin synthase deficiency, a rare inborn error of metabolism that results in decreased levels of tetrahydrobiopterin. This deficiency can cause hyperphenylalaninemia due to impaired hydroxylation of phenylalanine, and may also affect the synthesis of neurotransmitters, leading to various neurological symptoms. Symptoms of PTS deficiency can include intellectual disability, seizures, movement disorders, and behavioral problems. Early diagnosis and treatment with BH4 supplements and dietary management can improve outcomes for individuals with this condition.

Genetic and Molecular Biology

The PTS gene is located on chromosome 11 in humans. The enzyme itself is composed of several amino acids and has a specific three-dimensional structure that is essential for its function. Research into the molecular biology of PTS and its gene has provided insights into the mechanisms underlying BH4-related disorders and has opened up potential avenues for therapeutic intervention.

See Also

• Tetrahydrobiopterin deficiency
• Phenylketonuria
• Dihydropteridine reductase