GTP cyclohydrolase 1 feedback regulatory protein (GCHFR)

GTP cyclohydrolase 1 feedback regulatory protein (GCHFR) is a regulatory enzyme found in humans, encoded by the GCHFR gene. Its principal role is to modulate the activity of GTP cyclohydrolase I (GCH1), the first and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4). GCHFR forms oligomeric complexes with GCH1, mediating inhibition when bound to BH4 and activation in the presence of phenylalanine. Through this metabolic-sensing mechanism, GCHFR influences phenylalanine metabolism, the synthesis of biogenic amine neurotransmitters (such as dopamine and serotonin), and the production of nitric oxide. Genetic mutations or disruptions in this pathway are implicated in diseases involving neurotransmitter metabolism, including forms of hyperphenylalaninemia and phenylketonuria. Structural studies have revealed the molecular basis of its allosteric regulation, supporting its potential as a therapeutic target in disorders where BH4 metabolism is relevant.

Other names

GCHFRGFRPHsT16933P35GTP cyclohydrolase I feedback regulatorGTP cyclohydrolase I feedback regulatory protein

GCHFR allosterically inhibits GTP cyclohydrolase I via BH4 binding and allosterically activates it via L-phenylalanine binding.