title: Differences in oxygen-dependent nitric oxide metabolism by cytoglobin and myoglobin account for their differing functional roles.
abstract: The endogenous vasodilator nitric oxide (NO) is metabolized in tissues in an oxygen-dependent manner. In skeletal and cardiac muscle, high concentrations of myoglobin (Mb) function as a potent NO scavenger. However, the Mb concentration is very low in vascular smooth muscle, where low concentrations of cytoglobin (Cygb) may play a major role in metabolizing NO. Questions remain regarding how low concentrations of Cygb and Mb differ in terms of NO metabolism, and the basis for their different cellular roles and functions. In this study, electrode techniques were used to perform comparative measurements of the kinetics of NO consumption by Mb and Cygb. UV/Vis spectroscopic methods and computer simulations were performed to study the reaction of Mb and Cygb with ascorbate (Asc) and the underlying mechanism. It was observed that the initial rate of Cygb(3+) reduction by Asc was 415-fold greater than that of Mb(3+). In the low [O2] range (0-50 μM), the Cygb-mediated NO consumption rate is ~ 500 times more sensitive to changes in O2 concentration than that of Mb. The reduction of Cygb(3+) by Asc follows a reversible kinetic model, but that of Mb(3+) is irreversible. A reaction mechanism for Cygb(3+) reduction by Asc is proposed, and the reaction equilibrium constants are determined. Our results suggest that the rapid reduction of Cygb by cellular reductants enables Cygb to efficiently regulate NO metabolism in the vascular wall in an oxygen-dependent manner, but the slow rate of Mb reduction does not show this oxygen dependence.
authors.affiliation: Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA. Xiaoping.liu@osumc.edu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.forename: Jianjing
authors.initials: J
authors.lastname: Tong
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Zweier
authors.forename: Douglas
authors.initials: D
authors.lastname: Follmer
authors.forename: Craig
authors.initials: C
authors.lastname: Hemann
authors.forename: Raed S
authors.initials: RS
authors.lastname: Ismail
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
mesh_terms: D000465:Algorithms; D001205:Ascorbic Acid / Q000737:chemistry; D003198:Computer Simulation; D000078842:Cytoglobin; D005914:Globins / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D009211:Myoglobin / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D009211:Myoglobin; D016877:Oxidants; D009569:Nitric Oxide; D005914:Globins; D001205:Ascorbic Acid; D010100:Oxygen
keywords: cytoglobin; metabolism kinetics; myoglobin; nitric oxide; oxygen