- Mechanistic studies on the reaction of nitrocobalamin with glutathione: Kinetic evidence for formation of an aquacobalamin intermediate
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The essential but also toxic gaseous signaling molecule nitric oxide is scavenged by the reduced vitamin B12 complex cob(II)alamin. The resulting complex, nitroxylcobalamin [NO--Cbl(III)], is rapidly oxidized to nitrocobalamin (NO2Cbl) in the presence of oxygen; however, it is unlikely that nitrocobalamin is itself stable in biological systems. Kinetic studies on the reaction between NO2Cbl and the important intracellular antioxidant, glutathione (GSH), are reported. In this study, a reaction pathway is proposed in which the β-axial ligand of NO2Cbl is first substituted by water to give aquacobalamin (H 2OCbl+), which then reacts further with GSH to form glutathionylcobalamin (GSCbl). Independent measurements of the four associated rate constants k1, k-1, k2, and k-2 support the proposed mechanism. These findings provide insight into the fundamental mechanism of ligand substitution reactions of cob(III)alamins with inorganic ligands at the β-axial site. Kinetic studies on the reaction of nitrocobalamin (NO2Cbl) with glutathione show that glutathionylcobalamin (GSCbl) is formed via an aquacobalamin (H 2OCbl+) intermediate. This reaction pathway is demonstrated by independently determining individual rate constants for each step.
- Walker, David T.,Dassanayake, Rohan S.,Garcia, Kamille A.,Mukherjee, Riya,Brasch, Nicola E.
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