Pathway
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
Tetrahydrobiopterin (BH4) is an essential co-factor for the aromatic amino acid hydroxylases and glycerol ether monooxygenase and it regulates nitric oxide synthase (NOS) activity. Inherited BH4 deficiency leads to hyperphenylalaninemia, and dopamine and neurotransmitter deficiency in the brain. BH4 maintains enzymatic coupling to L-arginine oxidation to produce NO. Oxidation of BH4 to BH2 results in NOS uncoupling, resulting in superoxide (O2.-) formation rather than NO. Superoxide rapidly reacts with NO to produce peroxynitrite which can further uncouple NOS.
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These reactive oxygen species (superoxide and peroxynitrite) can contribute to increased oxidative stress in the endothelium leading to atherosclerosis and hypertension. The synthesis, recycling and effects of BH4 are shown here. Three enzymes are required for the de novo biosynthesis of BH4 and two enzymes for the recycling of BH4.
What the reference databases state
Statements
10 statements
10 statements · 1 reference database · Subject: Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation · Sources: Reactome
- AKT1 participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- CALM1 participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- DHFR participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- GCH1 participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- GCHFR participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- HSP90AA1 participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- NOS3 participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- PRKG2 participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- PTS participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only
- SPR participates in Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationProteinReactome R-HSA-1474151Inferred only