Dihydrobiopterin

Dihydrobiopterin, abbreviated BH2, is the dihydro (partially reduced) form of biopterin, a pteridine compound that serves as a cofactor in several enzymatic hydroxylation reactions. In biochemistry, the tetrahydro form of biopterin (BH4) is the more reduced and active cofactor, while BH2 is its oxidized product produced when BH4 donates electrons during hydroxylation.

In mammals, BH4-dependent enzymes include phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase. During these reactions, BH4 is oxidized to BH2 as the substrate is hydroxylated. The cellular cofactor pool is maintained by dihydropteridine reductase (DHPR), which uses NADH or NADPH to reduce BH2 back to BH4, thereby regenerating the active cofactor for continued catalysis. The balance between BH4 and BH2 reflects the redox state of the cell and the capacity to sustain monooxygenase activities.

Clinically, disruptions in BH4 regeneration can lead to impaired synthesis of catecholamines and serotonin, as well as elevated phenylalanine levels. Dihydropteridine reductase deficiency is a genetic disorder that causes malignant phenylketonuria due to insufficient regeneration of BH4, with associated neurotransmitter deficiencies. Treatment approaches often involve BH4 supplementation and replacement of deficient neurotransmitters. The BH2/BH4 cycle is thus central to amino acid metabolism and neurotransmitter production in humans.