title: Glutathione-dependent one-electron transfer reactions catalyzed by a B₁₂ trafficking protein.
abstract: CblC is involved in an early step in cytoplasmic cobalamin processing following entry of the cofactor into the cytoplasm. CblC converts the cobalamin cargo arriving from the lysosome to a common cob(II)alamin intermediate, which can be subsequently converted to the biologically active forms. Human CblC exhibits glutathione (GSH)-dependent alkyltransferase activity and flavin-dependent reductive decyanation activity with cyanocobalamin (CNCbl). In this study, we discovered two new GSH-dependent activities associated with the Caenorhabditis elegans CblC for generating cob(II)alamin: decyanation of CNCbl and reduction of aquocobalamin (OH2Cbl). We subsequently found that human CblC also catalyzes GSH-dependent decyanation of CNCbl and reduction of OH2Cbl, albeit efficiently only under anaerobic conditions. The air sensitivity of the human enzyme suggests interception by oxygen during the single-electron transfer step from GSH to CNCbl. These newly discovered GSH-dependent single-electron transfer reactions expand the repertoire of catalytic activities supported by CblC, a versatile B12-processing enzyme.
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0600.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0600.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gherasim
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0600.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Lesniak
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0600 rbanerje@umich.edu.
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D001483:Base Sequence; D002384:Catalysis; D017931:DNA Primers; D004579:Electron Transport; D005978:Glutathione / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D013438:Sulfhydryl Compounds; D005978:Glutathione; D014805:Vitamin B 12
keywords: Adenosylcobalamin (AdoCbl); Enzyme Mechanism; Glutathione; Redox; Vitamin; Vitamin B12
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