Quinoid dihydropteridine reductase (QDPR)

Quinoid dihydropteridine reductase (QDPR) is an enzyme that catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin, playing an essential role in the recycling of tetrahydrobiopterin (BH4), a critical cofactor for amino acid metabolism and neurotransmitter biosynthesis. QDPR deficiency impairs the regeneration of BH4, resulting in insufficient tyrosine and neurotransmitter production, and causing severe neurological symptoms, including developmental delay, intellectual disability, seizures, and movement disorders. Mutations in the QDPR gene cause dihydropteridine reductase deficiency, a rare inherited metabolic disorder accounting for about one-third of all cases of tetrahydrobiopterin deficiency syndromes. The enzyme is classified in the short chain dehydrogenase/reductase (SDR) family and is critical for maintaining the metabolic homeostasis of phenylalanine and neurotransmitter pathways, with potential links to neurodegeneration and oncogenesis when mutated.

Other names

Dihydropteridine reductaseDHPRSDR33C1PKU2HDHPRShort chain dehydrogenase/reductase family 33C member 16,7-dihydropteridine reductasetestis secretory sperm-binding protein Li 236P

Mechanism of action for drugs targeting the consequences of QDPR deficiency includes cofactor supplementation (to restore BH4 levels), precursor supplementation (to bypass dopamine or serotonin synthesis block), and dietary restriction (to reduce phenylalanine load). No small molecule inhibitors/activators of QDPR are used as direct drugs; rather, therapies act on the pathophysiological consequences of enzyme deficiency.