Formation tetrahydrobiopterin role

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). 

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). 

The production of NO by NO-synthase (NOS) (Figure 12) involves two domains, a reductase which binds flavin and an oxygenase which comprises a heme unit to which the substrate L-arginine binds. Three different forms of NOS are known, an inducible (iNOS), an endothelial (eNOS) and a neuronal one (nNOS). The details of the arginine oxidation mechanism have been studied in recent years, but only at the level of free-radical formation as far as EPR is concerned, so that the heme related part has not been addressed in great detail since the last review. The free-radical part involves determination of not only NO but also the superoxide anion and the tetrahydrobiopterin radical, to name the most prominent representatives. For the purpose of the present context we only mention briefly some of the relevant investigations. The production of O2 from the nNOS oxygenase domain was reported, as was its release by iNOS and by eNOS. A review on this aspect has become available. The role of NO in relation ofNO and ONOO has been reviewed with respect to consequences in postischemic myocardium. The detection of the tetrahydrobiopterin radical in the first reaction cycle of eNOS and nNOS has been reported. The interplay... 

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