Tetrahydrobiopterin in nitric oxide synthase


  • Jesús Tejero,

    1. Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
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  • Dennis Stuehr

    Corresponding author
    1. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
    • Dennis J. Stuehr, Department of Pathobiology (NC-22), The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
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  • Abbreviations: CaM, calmodulin; eNOS, endothelial nitric oxide synthase; FAD, flavin adenine dinucleotide; FMN, flavin mononucleotide; H2B, 7,8-dihydrobiopterin; H4B, (6R-)5,6,7,8-tetrahydrobiopterin; H4F, tetrahydrofolate; iNOS, inducible nitric oxide synthase; NADPH, nicotinamide adenine dinucleotide phosphate; nNOS, neuronal nitric oxide synthase; NOHA, Nω-hydroxy arginine; NOS, nitric oxide synthase


Summary: Nitric oxide synthase (NOS) is a critical enzyme for the production of the messenger molecule nitric oxide (NO) from L-arginine. NOS enzymes require tetrahydrobiopterin as a cofactor for NO synthesis. Besides being one of the few enzymes to use this cofactor, the role of tetrahydrobiopterin in NOS catalytic mechanism is different from other enzymes: during the catalytic cycle of NOS, tetrahydrobiopterin forms a radical species that is again reduced, thus effectively regenerating after each NO synthesis cycle. In this review, we summarize our current knowledge about the role of tetrahydrobiopterin in the structure, function, and catalytic mechanism of NOS enzymes. © 2013 IUBMB Life 65(4):358–365, 2013.