meso-Bromination of cyano- and aquacobalamins facilitates their processing into Co(II)-species by glutathione.
J Biol Inorg Chem
; 28(6): 571-581, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37479902
ABSTRACT
Cyanocobalamin (CNCbl), a medicinal form of vitamin B12, is resistant to glutathione (GSH), and undergoes intracellular processing via reductive decyanation producing the Co(II)-form of Cbl (Cbl(II)) mediated by the CblC-protein. Alteration of the CblC-protein structure might inhibit CNCbl processing. Here, we showed that introducing a bromine atom to the C10-position of the CNCbl corrin ring facilitates its reaction with GSH leading to the formation of Cbl(II) and cyanide dissociation. In a neutral medium, the reaction between C10-Br-CNCbl and GSH proceeds via the complexation of the reactants further leading to dimethylbenzimidazole (DMBI) substitution and electron transfer from GSH to the Co(III)-ion. The reaction is accelerated upon the GSH thiol group deprotonation. The key factors explaining the higher reactivity of C10-Br-CNCbl compared with unmodified CNCbl towards GSH are increasing the electrode potential of CNCbl two-electron reduction upon meso-bromination and the substantial labilization of DMBI, which was shown by comparing their reactions with cyanide and the pKa values of DMBI protonation (pKa base-off). Aquacobalamin (H2OCbl) brominated at the C10-position of the corrin reacts with GSH to give Cbl(II) via GSH complexation and subsequent reaction of this complex with a second GSH molecule, whereas unmodified H2OCbl generates glutathionyl-Cbl, which is resistant to further reduction by GSH.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina B 12
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Halogenação
Idioma:
En
Revista:
J Biol Inorg Chem
Ano de publicação:
2023
Tipo de documento:
Article