Obeid Rima, Fedosov Sergey N, Nexo Ebba
Aarhus Institute of Advanced Studies, , University of Aarhus, Aarhus, Denmark.
Department of Clinical Chemistry, University Hospital of the Saarland, Homburg, Germany.
Mol Nutr Food Res. 2015 Jul;59(7):1364-72. doi: 10.1002/mnfr.201500019. Epub 2015 May 12.
Methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) are coenzymes for methionine synthase and methylmalonyl-CoA mutase, respectively. Hydroxylcobalamin (HOCbl) and cyanocobalamin (CNCbl) are frequently used for supplementation. MeCbl and AdoCbl have recently emerged as alternative forms in supplements. In the light of metabolic transformation of Cbl into its cofactor forms, this review discusses current evidence on efficacy and utility of different Cbl forms in preventing or treating Cbl deficiency. Cbl-transporting proteins bind and mediate the uptake of all aforementioned forms of Cbl. After internalization and lysosomal release, Cbl binds to the cytosolic chaperon MMACHC that is responsible for (i) flavin-dependent decyanation of [CN-Co(3+) Cbl to [Co(2+)]Cbl; (ii) glutathione-dependent dealkylation of MeCbl and AdoCbl to [Co(2+/1+)]Cbl; and (iii) glutathione-dependent decyanation of CNCbl or reduction of HOCbl under anaerobic conditions. MMACHC shows a broad specificity for Cbl forms and supplies the Cbl(2+) intermediate for synthesis of MeCbl and AdoCbl. Cobalamin chemistry, physiology, and biochemistry suggest that MeCbl and AdoCbl follow the same route of intracellular processing as CNCbl does. We conclude that supplementing MeCbl or AdoCbl is unlikely to be advantageous compared to CNCbl. On the other hand, there are obvious advantages of high parenteral doses (1-2 mg) of HOCbl in treating inborn errors of Cbl metabolism.
甲钴胺（MeCbl）和腺苷钴胺（AdoCbl）分别是甲硫氨酸合成酶和甲基丙二酰辅酶A变位酶的辅酶。羟钴胺（HOCbl）和氰钴胺（CNCbl）常用于补充。MeCbl和AdoCbl最近已成为补充剂中的替代形式。鉴于钴胺素（Cbl）向其辅因子形式的代谢转化，本综述讨论了不同Cbl形式在预防或治疗Cbl缺乏症方面的疗效和实用性的现有证据。Cbl转运蛋白结合并介导所有上述Cbl形式的摄取。内化和溶酶体释放后，Cbl与胞质伴侣蛋白MMACHC结合，MMACHC负责：（i）[CN-Co(3+) Cbl的黄素依赖性脱氰作用生成[Co(2+)]Cbl；（ii）MeCbl和AdoCbl的谷胱甘肽依赖性脱烷基作用生成[Co(2+/1+)]Cbl；以及（iii）厌氧条件下CNCbl的谷胱甘肽依赖性脱氰作用或HOCbl的还原作用。MMACHC对Cbl形式具有广泛的特异性，并为MeCbl和AdoCbl的合成提供Cbl(2+)中间体。钴胺素的化学、生理学和生物化学表明，MeCbl和AdoCbl在细胞内的加工途径与CNCbl相同。我们得出结论，与CNCbl相比，补充MeCbl或AdoCbl不太可能具有优势。另一方面，高剂量（1-2mg）肠外注射HOCbl在治疗Cbl代谢先天性缺陷方面具有明显优势。
