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Differences in oxygen‐dependent nitric oxide metabolism by cytoglobin and myoglobin account for their differing functional roles
Author(s) -
Liu Xiaoping,
Tong Jianjing,
Zweier Joseph R.,
Follmer Douglas,
Hemann Craig,
Ismail Raed S.,
Zweier Jay L.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12352
Subject(s) - myoglobin , nitric oxide , chemistry , metabolism , oxygen , biochemistry , hemeprotein , oxygen metabolism , biophysics , biology , enzyme , heme , organic chemistry
The endogenous vasodilator nitric oxide ( NO ) is metabolized in tissues in an oxygen‐dependent manner. In skeletal and cardiac muscle, high concentrations of myoglobin ( M b) function as a potent NO scavenger. However, the M b concentration is very low in vascular smooth muscle, where low concentrations of cytoglobin ( C ygb) may play a major role in metabolizing NO . Questions remain regarding how low concentrations of C ygb and M b 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 M b and C ygb. UV / V is spectroscopic methods and computer simulations were performed to study the reaction of M b and C ygb with ascorbate ( A sc) and the underlying mechanism. It was observed that the initial rate of C ygb 3+ reduction by A sc was 415‐fold greater than that of M b 3+ . In the low [ O 2 ] range (0–50 μ m ), the Cygb‐mediated NO consumption rate is ~ 500 times more sensitive to changes in O 2 concentration than that of M b. The reduction of C ygb 3+ by A sc follows a reversible kinetic model, but that of M b 3+ is irreversible. A reaction mechanism for C ygb 3+ reduction by A sc is proposed, and the reaction equilibrium constants are determined. Our results suggest that the rapid reduction of C ygb by cellular reductants enables C ygb to efficiently regulate NO metabolism in the vascular wall in an oxygen‐dependent manner, but the slow rate of M b reduction does not show this oxygen dependence.