6-pyruvoyltetrahydropterin synthase (PTS)

6-pyruvoyltetrahydropterin synthase (PTS) is an enzyme essential for the second step in the biosynthesis of tetrahydrobiopterin (BH4), a crucial cofactor for aromatic amino acid hydroxylases and nitric oxide synthases[1][2][3][4][5]. PTS catalyzes the conversion of 7,8-dihydroneopterin triphosphate to 6-pyruvoyltetrahydropterin[3][4]. Deficiency in this enzyme, usually due to mutations in the PTS gene, is the most common cause of tetrahydrobiopterin deficiency, leading to hyperphenylalaninemia and deficits in neurotransmitter synthesis, manifesting as developmental delay, neurological impairment, and, in some cases, severe intellectual disability and seizures[1][3][5]. PTS is a cytoplasmic enzyme, typically forming a hexameric structure, and is classified as an enzyme (lyase)[3][4]. Clinical management of its deficiency involves BH4 supplementation and, when warranted, neurotransmitter precursors[1][5].

Other names

6-pyruvoyl tetrahydrobiopterin synthasePTP synthasePTPSsepiapterin synthase Asepiapterin synthesizing enzyme 1PTPS_HUMAN

Replacement therapy (BH4/Sapropterin) to compensate for BH4 deficiency due to lack of PTS activity; Potential inhibition of PTS activity (e.g., by Mycophenolate mofetil, mechanism not fully characterized)[2]