biopterin

Biopterin is a pteridine derivative and the fully oxidized parent compound of the reduced cofactor tetrahydrobiopterin (BH4). In many organisms BH4 acts as an essential cofactor for enzymes involved in the synthesis of neurotransmitters and nitric oxide. The pterin pool, which includes biopterin, dihydrobiopterin (BH2), and BH4, interconverts through cellular redox reactions, and BH2 and biopterin can be regenerated back to BH4 by dihydropteridine reductase using NADPH.

Biopterin-related cofactors support several key enzymes. The best known are the aromatic amino acid hydroxylases—phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase—which convert phenylalanine to tyrosine, tyrosine to L-DOPA, and tryptophan to serotonin precursors. Nitric oxide synthases, which produce nitric oxide, also require BH4 for proper catalysis. Adequate BH4 availability is essential for normal neurotransmitter production and nitric oxide signaling; oxidation to BH2 or biopterin can diminish enzyme activity unless BH4 is recycled.

Biosynthesis and recycling of BH4 begin with the de novo pathway from GTP, with GTP cyclohydrolase I as the first step. This is followed by 6-pyruvoyl-tetrahydropterin synthase and sepiapterin reductase to yield BH4. A salvage pathway and recycling via dihydropteridine reductase help maintain BH4 levels by reducing oxidized pterins back to BH4.

In research and clinical settings, biopterin and related pterins are measured as biomarkers of pterin metabolism, immune activation, and oxidative stress. Defects in BH4 synthesis or recycling can cause hyperphenylalaninemia and neurotransmitter deficiencies, sometimes treated with BH4 supplementation and neurotransmitter replacement strategies.