Biological Activity of Pseudovitamin B12on Cobalamin-Dependent Methylmalonyl-CoA Mutase and Methionine Synthase in Mammalian Cultured COS-7 Cells
Biological Activity of Pseudovitamin B12on Cobalamin-Dependent Methylmalonyl-CoA Mutase and Methionine Synthase in Mammalian Cultured COS-7 Cells
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DOI：
10.3390/molecules25143268
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发表时间：
2020-07-01
期刊：
影响因子：
4.6
通讯作者：
Watanabe, Fumio
中科院分区：
文献类型：
--
作者：
Bito, Tomohiro;Bito, Mariko;Watanabe, Fumio
腺苷钴酰胺（俗称假维生素B-12）由肠道细菌合成或从食用蓝藻中摄取。假维生素 B(12) 对哺乳动物细胞中钴胺素依赖性酶活性的影响尚未得到充分研究。本研究旨在研究假维生素 B(12) 对培养的哺乳动物 COS-7 细胞中哺乳动物维生素 B-12 依赖性酶蛋氨酸合酶和甲基丙二酸单酰辅酶 A 变位酶活性的影响，以确定假维生素 B(12) 是否充当这些酶的抑制剂或辅助因子。尽管假维生素 B(12) 的羟基形式在培养细胞中充当甲硫氨酸合酶的辅酶，但与维生素 B(12) 的羟基形式不同，假维生素 B(12) 不会激活甲硫氨酸合酶的翻译。在第二个酶促反应中，假维生素 B(12) 的腺苷形式不充当辅酶或甲基丙二酰辅酶 A 变位酶的抑制剂。使用人转钴胺素 II 进行细胞摄取实验，结果表明用大量假维生素 B(12) 处理可能会抑制转钴胺素 II 介导的培养基中存在的生理微量浓度维生素 B(12) 的吸收。
Adenyl cobamide (commonly known as pseudovitamin B-12) is synthesized by intestinal bacteria or ingested from edible cyanobacteria. The effect of pseudovitamin B(12)on the activities of cobalamin-dependent enzymes in mammalian cells has not been studied well. This study was conducted to investigate the effects of pseudovitamin B(12)on the activities of the mammalian vitamin B-12-dependent enzymes methionine synthase and methylmalonyl-CoA mutase in cultured mammalian COS-7 cells to determine whether pseudovitamin B(12)functions as an inhibitor or a cofactor of these enzymes. Although the hydoroxo form of pseudovitamin B(12)functions as a coenzyme for methionine synthase in cultured cells, pseudovitamin B(12)does not activate the translation of methionine synthase, unlike the hydroxo form of vitamin B(12)does. In the second enzymatic reaction, the adenosyl form of pseudovitamin B(12)did not function as a coenzyme or an inhibitor of methylmalonyl-CoA mutase. Experiments on the cellular uptake were conducted with human transcobalamin II and suggested that treatment with a substantial amount of pseudovitamin B(12)might inhibit transcobalamin II-mediated absorption of a physiological trace concentration of vitamin B(12)present in the medium.