Clarification of the mechanism of menaquinone-4 formation from naphthoquinone ring and isoprenoid side-chain in major tissues of rats

阐明大鼠主要组织中萘醌环和类异戊二烯侧链形成甲基萘醌-4 的机制

基本信息

  • 批准号:
    07660150
  • 负责人:
  • 金额:
    $ 1.47万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1995
  • 资助国家:
    日本
  • 起止时间:
    1995 至 1996
  • 项目状态:
    已结题

项目摘要

Phylloquinone (PK=VK_1) and the menaquinones (MK-n, VK_2) are naturally occurring forms of vitamin K.Most of the menaquinone series are synthesized microbiologically, but we have reported elsewhere that menaquinone-4 (MK-4) is an usual in being synthesized by the conversion of ingested phylloquinone or menadione (VK_3) in the major tissues of germ-free rats or mice (which lack an intestinal microflora). The present research was undertaken to clarify the mechanism of MK-4 formation from naphthoquinone ring and isoprenoid side-chain in major tissues of rats.In the first experiment, the distribution of phylloquinone and MK-4 in various tissues were assessed after the oral administration of phylloquinone. Wistar rats were fed a vitamin-K-deficient diet for 9 days, fasted for 24h and then given phylloquinoe orally at 4mg/kg body weight. Rats were sacrificed 0,6,12, and 24h after the administration, and an analysis was made of the vitamin K analogues in the plasma, liver, brain, testis, kidn … More ey, and spleen. The phylloquinone concentration in plasma and the tissues reached a peak 6h after the oral administration of phylloquinone. By contrast, the concentration of MK-4 peaked in the liver, plasma, kidney, and spleen at 12h, and in brain and testis at 24h. This data suggests that the ingested phylloquinone was probably converted into MK-4 within the tissues themselves, rather than via hepatic metabolism. The evidence for this is that, after phylloquinone administration, (i) in each of the tissues, the MK-4 concentration increased much more slowly than that of phylloquinone, and (ii) the MK-4 concentration in the plasma and liver reached only much lower levels than those seen in other tissues.In the second and third experiments in which the labeled phylloquinone was used, it was shown that [side-chain-^3H]-label of phylloquinone was not incorporated into the side-chain of MK-4, however, the radioacitivity originated from the [ring-8]-^<14>C-phylloquinone was detected in the MK-4 fraction of various tissues. These phenomena indicate that the isoprenoid side-chain of phylloquinone once separate from its maphthoquinone ring, then it may be replaced by other isoprenoid side chain such as geranyl-geranyl group within each tissue, and suggest that K_3 must be detected in the midst of the reaction. Actually, the radioactivity from [ring-8]-^<14>C-phylloquinone was clearly detected in the K_3 fraction of heart. In the final experiment, the converted MK-4 fraction was collected and purified, then the identification of estimated MK-4 molecule was undertaken by the high-resolution mass spectrometry, and it was finally identified as MK-4. Less
叶绿醌(PK=VK_1)和甲基萘醌(MK-n、VK_2)是维生素K的天然存在形式。大多数甲基萘醌系列是由微生物合成的,但我们在别处报道过甲基萘醌-4(MK-4)通常是由摄入的叶绿醌或甲基萘醌(VK_3)在无菌大鼠或小鼠(缺乏肠道菌群)的主要组织中转化而合成的。本研究旨在阐明MK-4在大鼠主要组织中由萘醌环和类异戊二烯侧链形成的机制。在第一个实验中,口服叶绿醌后,评估叶绿醌和MK-4在各组织中的分布。用维生素K缺乏饲料喂养Wistar大鼠9天,禁食24小时,然后以4 mg/kg体重口服叶醌。分别于给药后0、6、12、24 h处死大鼠,测定血浆、肝、脑、睾丸、肾、脑、肾、脑、肾、肾 ...更多信息 眼睛和脾脏口服叶绿醌后6 h,血浆和组织中叶绿醌浓度达到峰值。MK-4在肝脏、血浆、肾脏和脾脏中的浓度在12 h达到峰值,在脑和睾丸中的浓度在24 h达到峰值。这些数据表明,摄入的叶绿醌可能在组织本身内转化为MK-4,而不是通过肝脏代谢。这方面的证据是,在给予叶绿醌后,(i)在每个组织中,MK-4浓度的增加比叶绿醌的增加慢得多,和(ii)血浆和肝脏中的MK-4浓度仅达到比在其它组织中观察到的水平低得多的水平。结果表明,叶绿醌的[侧链-^3H]-标记物未掺入MK-4的侧链中,然而,<14>在各种组织的MK-4组分中检测到源自[环-8]-^3C-叶绿醌的放射性。这些现象表明,叶绿醌的类异戊二烯侧链一旦从其梅菲醌环上脱离,就可能被其它的类异戊二烯侧链如香叶基-香叶基所取代,并提示在反应过程中必须检测到K_3。实际上,[ring-8]-^<14>C-叶绿醌的放射性在心脏的K_3组分中被清楚地检测到。在最后的实验中,收集并纯化转化的MK-4级分,然后通过高分辨率质谱法对估计的MK-4分子进行鉴定,最终鉴定为MK-4。少

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yamamoto, R., Komai, M., Kojima, K., Furukawa, Y., and Kimura, S.: ""Menaquinone-4 accumulation in various tissues after an oral administration of phylloquinone in Wistar rats."" J.Nutr. Sci. Vitaminol.43-1 (in press). 133-143 (1997)
Yamamoto, R.、Komai, M.、Kojima, K.、Furukawa, Y. 和 Kimura, S.:“Wistar 大鼠口服叶绿醌后,Menaquinone-4 在各种组织中的积累。”J.Nutr
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
  • 作者:
  • 通讯作者:
駒井 三千夫: "ビタミンの事典(「腸内細菌によるビタミンKの産生」(分担)" 日本ビタミン学会編(朝倉書店), 522 (1996)
小牧道夫:《维生素百科全书(“肠道细菌生产维生素 K”(合作)》,日本维生素学会编(朝仓书店),522(1996 年)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
小嶋浩揮、駒井三千夫、他: "ビタミンK_1,K_3投与後のMK-4濃度の経時的変化" ビタミン. 70・(4). 192-192 (1996)
Hiroki Kojima、Michio Komai 等:“施用维生素 K_1 和 K_3 后 MK-4 浓度的时间变化”维生素 70・(4) (1996)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
小嶋浩揮、駒井三千夫、他: "ビタミンK欠乏ラットにおけるK類の生理活性の比較" ビタミン. 69・(4). 260-260 (1995)
Hiroki Kojima、Michio Komai 等:“维生素 K 缺乏大鼠中 K 物种的生理活性比较”维生素 69・(4) (1995)。
  • DOI:
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  • 影响因子:
    0
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KOMAI Michio其他文献

KOMAI Michio的其他文献

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{{ truncateString('KOMAI Michio', 18)}}的其他基金

Cancer risk assessment study on gene polymorphism of bitter taste receptor TAS2R38 and glutathione-S-transferase by analyzing ToMMo data
通过分析ToMMo数据进行苦味受体TAS2R38和谷胱甘肽-S-转移酶基因多态性的癌症风险评估研究
  • 批准号:
    18K18442
  • 财政年份:
    2018
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Clarification of dietary zinc signal transduction through the intestine to the appetite control region of brain.
澄清膳食锌信号通过肠道转导至大脑食欲控制区域。
  • 批准号:
    20380072
  • 财政年份:
    2008
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Physiological study on the role of zinc enzyme on the improvement of taste disorders
锌酶改善味觉障碍作用的生理研究
  • 批准号:
    15380087
  • 财政年份:
    2003
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Clarification of a novel physiological function of menaquinone-4 (vitamin K2), a postulated active form of vitamin K in various tissues
澄清 Menaquinone-4(维生素 K2)的新生理功能,这是维生素 K 在多种组织中的一种假定活性形式
  • 批准号:
    13660115
  • 财政年份:
    2001
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Clarification of the conversion mechanism of vitamin K analogues to menaquinone-4, a potent hormone-like substance, in the rat tissues.
阐明维生素 K 类似物在大鼠组织中向 Menaquinone-4(一种强效激素样物质)的转化机制。
  • 批准号:
    11660119
  • 财政年份:
    1999
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Menaquinone-4, a potent anti-osteoporosis vitamin : Clarification of its intracellular distribution and new physiological function
Menaquinone-4,一种有效的抗骨质疏松维生素:阐明其细胞内分布和新的生理功能
  • 批准号:
    09660127
  • 财政年份:
    1997
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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