Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product.
Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product.
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DOI：
10.1016/j.ymgme.2009.04.005
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发表时间：
2009-08
影响因子：
3.8
通讯作者：
Jacobsen, Donald W.
中科院分区：
文献类型：
--
作者：
Hannibal, Luciana;Kim, Jihoe;Brasch, Nicola E.;Wang, Sihe;Rosenblatt, David S.;Banerjee, Ruma;Jacobsen, Donald W.
关键词：
CblC互补组的MMACHC基因产物被称为cblC蛋白，它催化氰钴胺(维生素B12)的体外和体内脱氰反应。我们推测，cblC蛋白还将催化新内化的甲钴胺(MeCbl)和5‘-脱氧腺苷钴胺(ADOCbl)的脱烷基化，这是饮食中自然存在的烷基钴胺。在培养的内皮细胞中使用[57Co]-ADOCbl和MeCbl类似物验证了这一假设，这些类似物包括从C2(乙基钴胺)到C6(己基钴胺)的[57Co]标记的直链钴胺。[57Co]-ADOCbl被培养的牛主动脉内皮细胞转化为[57Co]-MeCbl，这表明可能是涉及cblC蛋白的脱烷基化过程去除了5‘-脱氧腺苷烷基。令人惊讶的是，所有的直链烷基钴蛋白都作为Adobe Cbl和MeCbl生物合成的底物。然后，对正常皮肤成纤维细胞和来自3名MMACHC基因突变患者的成纤维细胞进行了去烷基作用的评估。正常皮肤成纤维细胞很容易将[57Co]-丙基钴胺转化为[57Co]-ADOCbl和[57Co]-MeCbl，而cblC突变成纤维细胞则很少或没有转化。这些研究表明，CBLC蛋白在哺乳动物细胞中负责CNCbl(脱氰化)和烷基钴胺(脱烷基)的早期处理。
The MMACHC gene product of the cblC complementation group, referred to as the cblC protein, catalyzes the in vitro and in vivo decyanation of cyanocobalamin (vitamin B12). We hypothesized that the cblC protein would also catalyze the dealkylation of newly internalized methylcobalamin (MeCbl) and 5′-deoxyadenosylcobalamin (AdoCbl), the naturally occurring alkylcobalamins that are present in the diet. The hypothesis was tested in cultured endothelial cells using [57Co]-AdoCbl and MeCbl analogs consisting of [57Co]-labeled straight-chain alkylcobalamins ranging from C2 (ethylcobalamin) to C6 (hexylcobalamin). [57Co]-AdoCbl was converted to [57Co]-MeCbl by cultured bovine aortic endothelial cells, suggesting that a dealkylation process likely involving the cblC protein removed the 5′-deoxyadenosyl alkyl group. Surprisingly, all of the straight-chain alkylcobalamins served as substrates for the biosynthesis of both AdoCbl and MeCbl. Dealkylation was then assessed in normal skin fibroblasts and fibroblasts derived from 3 patients with mutations in the MMACHC gene. While normal skin fibroblasts readily converted [57Co]-propylcobalamin to [57Co]-AdoCbl and [57Co]-MeCbl, there was little or no conversion in cblC mutant fibroblasts. These studies suggest that the CblC protein is responsible for early processing of both CNCbl (decyanation) and alkylcobalamins (dealkylation) in mammalian cells.
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DOI：
10.1002/ajmg.1320330431
发表时间：
1989-08-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
SHIH, VE;AXEL, SM;ROSENBLATT, DS
通讯作者：
ROSENBLATT, DS
影响因子：
2.9
作者：
GIMSING, P;NEXO, E;HIPPE, E
通讯作者：
HIPPE, E
DOI：
10.1073/pnas.72.8.3181
发表时间：
1975-01-01
影响因子：
11.1
作者：
GRAVEL, RA;MAHONEY, MJ;ROSENBERG, LE
通讯作者：
ROSENBERG, LE
影响因子：
2.9
作者：
HOGENKAMP, HPC;BRATT, GT;SUN, S
通讯作者：
SUN, S
影响因子：
15
作者：
KIM, SH;CHEN, HL;HALPERN, J
通讯作者：
HALPERN, J