title: Exploring the redox reactions between heme and tetrahydrobiopterin in the nitric oxide synthases.
abstract: The NO synthases (NOSs) catalyze a two-step oxidation of L-arginine (Arg) to generate nitric oxide (NO) plus L-citrulline. Because NOSs are the only hemeproteins known to contain tetrahydrobiopterin (H4B) as a bound cofactor, the function and role of H4B in their heme-based oxygen activation and catalysis is of current interest. Distinct oxidative and reductive transitions of bound H4B cofactor occur during catalysis and are associated with distinct redox transitions of the NOS heme and flavin prosthetic groups. In this perspective, we discuss the redox transitions of H4B and heme with regard to their kinetics, regulation, role in the catalytic mechanism, and how and why they may be linked.
authors.affiliation: Lerner Research Institute, Cleveland Clinic, Ohio State University, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Stuehr
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Wei
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Russ
authors.initials: R
authors.lastname: Hille
mesh_terms: D000818:Animals; D001669:Biochemical Phenomena; D001671:Biochemistry; D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000737:chemistry* / Q000378:metabolism*; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D005609:Free Radicals; D001708:Biopterins; D009569:Nitric Oxide; D006418:Heme; D019001:Nitric Oxide Synthase; C003402:sapropterin