tetrahydropterin

Tetrahydropterin refers to a class of fully reduced pterin derivatives, in which the bicyclic pteridine ring system is saturated with hydrogens. The best-known member of this family is tetrahydrobiopterin (BH4), a key biological cofactor. Tetrahydropterins occur in many organisms and participate in redox biology and the metabolism of aromatic amino acids.

In mammals, BH4 is produced de novo from GTP through a multistep pathway involving GTP cyclohydrolase I, pyruvoyl tetrahydropterin synthase, and sepiapterin reductase. A salvage pathway regenerates BH4 from its oxidized forms via dihydropteridine reductase. During reactions, BH4 can be oxidized to dihydrobiopterin or further to biopterin, influencing cofactor availability and enzyme activity.

Biological role and importance are most evident in its function as a cofactor for aromatic amino acid hydroxylases—phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase—which initiate the synthesis of catecholamines and serotonin. BH4 is also required for proper activity of nitric oxide synthases, linking tetrahydropterins to nitric oxide signaling and vascular function. Consequently, BH4 status affects neurotransmitter production and cardiovascular physiology.

Clinical relevance arises from defects in BH4 metabolism or regeneration, such as dihydropteridine reductase deficiency, which can cause hyperphenylalaninemia and neurotransmitter imbalances. Sapropterin dihydrochloride (a synthetic BH4 form) is used therapeutically to enhance phenylalanine metabolism and support neurotransmitter synthesis in certain patients.

Other tetrahydropterins participate in related metabolic pathways and redox processes, underscoring the broader role of this class of compounds in biology.