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Mechanistic Studies on the Reaction of Nitrocobalamin with Glutathione: Kinetic Evidence for Formation of an Aquacobalamin Intermediate
Author(s) -
Walker David T.,
Dassanayake Rohan S.,
Garcia Kamille A.,
Mukherjee Riya,
Brasch Nicola E.
Publication year - 2013
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201300254
Subject(s) - chemistry , glutathione , ligand (biochemistry) , nitric oxide , reaction mechanism , stereochemistry , antioxidant , reaction rate constant , molecule , s nitrosoglutathione , redox , medicinal chemistry , computational chemistry , kinetics , inorganic chemistry , enzyme , biochemistry , organic chemistry , catalysis , receptor , physics , quantum mechanics
The essential but also toxic gaseous signaling molecule nitric oxide is scavenged by the reduced vitamin B 12 complex cob(II)alamin. The resulting complex, nitroxylcobalamin [NO – ‐Cbl(III)], is rapidly oxidized to nitrocobalamin (NO 2 Cbl) in the presence of oxygen; however, it is unlikely that nitrocobalamin is itself stable in biological systems. Kinetic studies on the reaction between NO 2 Cbl and the important intracellular antioxidant, glutathione (GSH), are reported. In this study, a reaction pathway is proposed in which the β‐axial ligand of NO 2 Cbl is first substituted by water to give aquacobalamin (H 2 OCbl + ), which then reacts further with GSH to form glutathionylcobalamin (GSCbl). Independent measurements of the four associated rate constants k 1 , k –1 , k 2 , 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.