| Autor: |
Dereven'kov IA; Ivanovo State University of Chemistry and Technology, Sheremetevskiy Str. 7, 153000, Ivanovo, Russian Federation. derevenkov@gmail.com., Osokin VS; Ivanovo State University of Chemistry and Technology, Sheremetevskiy Str. 7, 153000, Ivanovo, Russian Federation., Hannibal L; Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center-University of Freiburg, 79106, Freiburg, Germany., Makarov SV; Ivanovo State University of Chemistry and Technology, Sheremetevskiy Str. 7, 153000, Ivanovo, Russian Federation., Khodov IA; G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Akademicheskaya Str. 1, 153045, Ivanovo, Russian Federation., Koifman OI; Ivanovo State University of Chemistry and Technology, Sheremetevskiy Str. 7, 153000, Ivanovo, Russian Federation. |
| Abstrakt: |
Hypochlorous acid (HOCl) is a strong oxidant produced by myeloperoxidase. Previous work suggested that HOCl modifies the corrin ring of cobalamins to yield chlorinated species via mechanisms that are incompletely understood. Herein, we report a mechanistic study on the reaction between cyanocobalamin (CNCbl, vitamin B 12 ) and HOCl. Under weakly acidic, neutral and weakly alkaline conditions, the reaction produces the c-lactone derivative of CNCbl chlorinated at the C10-position of corrin ring (C10-Cl-CNCbl-c-lactone). Formation of C10-Cl-CNCbl-c-lactone was not observed at pH ≥ 9.9. The chlorination of CNCbl by HOCl proceeds via two pathways involving one and two HOCl molecules: the reaction is initiated by the very fast formation of a complex between CNCbl and HOCl, which either undergoes slow transformation to chlorinated species, or rapidly reacts with a second HOCl molecule to produce C10-Cl-CNCbl. Subsequent reaction of C10-Cl-CNCbl with HOCl proceeds rapidly toward lactone ring formation by H-atom abstraction at position C8. This work uncovered mechanisms and products of the reaction of a biologically active and therapeutically used cobalamin, CNCbl and the endogenous oxidant HOCl. Binding and reactivity studies of C10-Cl-CNCbl and C10-Cl-CNCbl-c-lactone with relevant proteins of the cobalamin pathway and with cultured cells are necessary to elucidate the potential physiological effects of these species. |
