Chu R C, Begley J A, Colligan P D, Hall C A
Department of Medicine, Albany Medical College, NY.
Metabolism. 1993 Mar;42(3):315-9. doi: 10.1016/0026-0495(93)90080-8.
The effect of supplying exogenous methylcobalamin (MeCbl), a methyl donor to methionine synthase (MS), on the cellular metabolism of MeCbl was tested in cultured fibroblasts from healthy persons and from a subject with an inherited defect in the synthesis of MeCbl. MeCbl bound to transcobalamin II (TCII) was taken up in larger amounts than cyanocobalamin (CN-Cbl), but was equal to the uptake of hydroxocobalamin (OH-Cbl). The form of Cbl in the lysosomes persisted as the same form, bound to TCII, to which the cells were exposed in the medium. Once released from the lysosomes, both MeCbl and OH-Cbl were converted in the same proportions to coenzyme forms, suggesting equivalent entry into common cellular pools of Cbl from which active forms are synthesized. Exogenous MeCbl enjoyed no advantage in binding to MS, in synthesis of MeCbl, and in supporting cell division in the absence of methionine. All evidence supported the concept that in human cells the active MeCbl on MS forms de novo on the enzyme. It appeared unlikely that therapeutic MeCbl would have any advantage over OH-Cbl in the treatment of MeCbl deficiency or Cbl deficiency in general.
向健康人和一名遗传性甲基钴胺素（MeCbl）合成缺陷患者的培养成纤维细胞中添加外源性甲硫氨酸合成酶（MS）的甲基供体甲基钴胺素（MeCbl），测试其对MeCbl细胞代谢的影响。与钴胺素（CN-Cbl）相比，与转钴胺素II（TCII）结合的MeCbl摄取量更大，但与羟钴胺素（OH-Cbl）的摄取量相当。溶酶体中的钴胺素（Cbl）形式保持不变，与细胞在培养基中接触的TCII结合。一旦从溶酶体中释放出来，MeCbl和OH-Cbl都以相同比例转化为辅酶形式，这表明它们以同等程度进入共同的细胞钴胺素池，从该池中合成活性形式。在缺乏甲硫氨酸的情况下，外源性MeCbl在与MS结合、MeCbl合成以及支持细胞分裂方面均无优势。所有证据都支持这样一个概念，即在人类细胞中，MS上的活性MeCbl是在该酶上从头形成的。在治疗MeCbl缺乏症或一般的钴胺素缺乏症时，治疗性MeCbl似乎不会比OH-Cbl有任何优势。
