Tetrahydrobiopterin redox cycling in nitric oxide synthase: evidence supports a through-heme electron delivery.

ABSTRACT: The nitric oxide synthases (NOS) catalyze a two-step oxidation of l-arginine (Arg) to generate NO. In the first step, O₂ activation involves one electron being provided to the heme by an enzyme-bound 6R-tetrahydro-l-biopterin cofactor (H₄ B), and the H₄ B radical must be reduced back to H₄ B in order for NOS to continue catalysis. Although an NADPH-derived electron is used to reduce the H₄ B radical, how this occurs is unknown. We hypothesized that the NOS flavoprotein domain might reduce the H₄ B radical by utilizing the NOS heme porphyrin as a conduit to deliver the electron. This model predicts that factors influencing NOS heme reduction should also influence the extent and rate of H₄ B radical reduction in kin

SUBMITTER: Ramasamy S 

PROVIDER: S-EPMC5387691 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature