The Role of Tetrahydrobiopterin in Nitric Oxide Synthase

Nitric oxide ( NO) was discovered as the endothelium-derived relaxation factor. It is produced in the central nervous system, lungs, macrophages, and vascular endothelial cells in response to a variety of stimuli. It initiates a cGM P 

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Griscavage, J. M., Fukuto, J. M., Komori, Y., and Ignarro, L. J. (1994). Nitric oxide inhibits neuronal nitric oxide synthase by interacting with the heme prosthetic group. Role of tetrahydrobiopterin in modulating the inhibitory action of nitric oxide. /. Biol. Chem. 269, 21644-21649. 

Klatt, P., Schmidt, K., Lehner, D., Clatter, O., Bachinger, H. P., and Mayer, B. (1995). Structural analysis of porcine brain nitric oxide synthase reveals a novel role of tetrahydrobiopterin and L-arginine in the formation of an SDS-resistant dimer. EMBO 7. (in press). 

Nitric oxide inhibits neuronal nitrie oxide synthase by interacting with the heme prosthetie group. Role of tetrahydrobiopterin in modulating the inhibitory action of nitric oxide. J Biol Chem 269 21644 21649... 

Tetrahydrobiopterin is not a vitamin, because it can be synthesized from GTP, as shown in Figure 10.2 (Thony et al., 2000). It is the coenzyme for mixed-function oxidases phenylalanine, tyrosine, and tryptophan hydroxylases alkyl glycerol monoxygenase, which catalyzes the cleavage of alkyl glycerol ethers and nitric oxide synthase in the formation of nitric oxide. In addition to its coenzyme role, tetrahydrobiopterin has a direct effect on neurons, acting to stimulate dopamine release via a cAMP-dependent protein kinase and a calcium channel (Koshimura et al., 2000). 

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