Comparative uptake, metabolism, and utilization of menaquinone-4 and phylloquinone in human cultured cell lines.
Comparative uptake, metabolism, and utilization of menaquinone-4 and phylloquinone in human cultured cell lines.
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DOI：
10.1016/j.bmc.2006.06.004
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发表时间：
2006-10
影响因子：
3.5
通讯作者：
Y. Suhara;Aya Murakami;K. Nakagawa;Yukari Mizuguchi;T. Okano
中科院分区：
文献类型：
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作者：
Y. Suhara;Aya Murakami;K. Nakagawa;Yukari Mizuguchi;T. Okano
人们普遍认为，维生素K在体内的利用率取决于其同系物，其生物活性在器官之间会有所不同。为了验证这一假设，我们研究了甲基萘醌-4（MK-4）和叶绿醌（PK）在两种培养的人细胞系（HepG 2和MG-63）中的摄取、代谢和利用。孵育1、3和6 h后，从细胞和培养基中制备脂质提取物。维生素K类似物（18 O-、16 O-醌和环氧化物形式）的检测采用LC-APCI-MS/MS进行，如先前所报告。在维生素K环氧化物的形成过程中，通过羧化催化反应，将维生素K中的18 O置换为大气中的16 O2。结果，在MK-4和PK之间观察到细胞摄取量的显著差异。与18 O标记的PK相比，18 O标记的MK-4被细胞迅速且显著良好地吸收，并通过氢醌形式代谢为环氧化物形式。MK-4和PK摄取的差异不受华法林治疗的影响，尽管两种化合物的代谢均受到显著抑制。该方法可用于阐明维生素K在靶细胞中的某些作用，并促进新的维生素K药物的开发。
It is generally accepted that the availability of vitamin K in vivo depends on its homologues, the biological activities of which would differ among organs. To test this hypothesis, we examined the uptake, metabolism, and utilization of menaquinone-4 (MK-4) and phylloquinone (PK) using18O-labeled compounds in two cultured human cell lines (HepG2 and MG-63). Lipid extracts were prepared from the cells and media after 1, 3, and 6h of incubation. The detection of the vitamin K analogues (18O-,16O-quinone, and epoxide forms) was carried out with LC-APCI-MS/MS as previously reported. The18O of vitamin K was replaced with atmospheric16O2during the formation of vitamin K epoxide with a carboxylative catalytic reaction. As a result, a significant difference was observed between MK-4 and PK in the amounts taken up into the cells. The18O-labeled MK-4 was rapidly and remarkably well absorbed into the cells and metabolized to the epoxide form via a hydroquinone form as compared to the18O-labeled PK. The difference in uptake of MK-4 and PK was not affected by treatment with warfarin although the metabolism of both compounds was markedly inhibited. This methodology should be utilized to clarify some of the actions of vitamin K in target cells and facilitate the development of new vitamin K drugs.