Reactome | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

Stable Identifier

R-HSA-1474151

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

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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.
These reactive oxygen species (superoxide and peroxynitrite) can contribute to increased oxidative stress in the endothelium leading to atherosclerosis and hypertension (Thony et al. 2000, Crabtree and Channon 2011,Schulz et al. 2008, Schmidt and Alp 2007). 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.

Literature References

PubMed ID	Title	Journal	Year
21550412	Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease Crabtree, MJ, Channon, KM	Nitric Oxide	2011
18321209	Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension Schulz, E, Jansen, T, Wenzel, P, Daiber, A, Münzel, T	Antioxid Redox Signal	2008
17555404	Mechanisms for the role of tetrahydrobiopterin in endothelial function and vascular disease Schmidt, TS, Alp, NJ	Clin Sci (Lond)	2007
10727395	Tetrahydrobiopterin biosynthesis, regeneration and functions Thöny, B, Auerbach, G, Blau, N	Biochem J	2000