The function and metabolism of vitamin K.
The function and metabolism of vitamin K.
复制标题
维生素K的功能和代谢。
DOI：
10.1146/annurev.nu.04.070184.001433
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发表时间：
1984
影响因子：
8.9
通讯作者：
Olson,RE
中科院分区：
文献类型：
--
作者：
Olson,RE
自从10年前发现γ-羧基谷氨酸以来，人们对维生素K的功能和代谢的认识取得了很大进展。这种新的氨基酸在不同来源的蛋白质中的分布以及维生素K依赖性羧化酶在不同组织中的存在，强调了一种新的三联体：维生素K、Gla和钙在生物学中的广泛意义。已经获得了关于维生素K的利用和再利用的重要性的新知识，维生素K的体内库对于脂溶性维生素来说是极低的，用于维生素K依赖性蛋白中肽结合的谷氨酸残基的翻译后羧化。通过药物和营养素调节维生素K-维生素K-环氧化物循环的活化似乎是控制维生素K依赖性蛋白质合成的关键，其中八种蛋白质参与血液凝固。维生素K依赖性γ-谷氨酰羧化酶的纯化比任何人想象的都要艰巨。许多关于其复杂机制的问题，因为它利用四种底物（KH 2，O 2，CO 2和含Glu的肽），直到酶是均匀的才能回答。基本上，维生素K依赖性羧化酶系统由与二氧化碳固定偶联的专门微粒体电子传递系统组成。该反应不需要ATP，但显然利用维生素KH 2氧化的能量来进行Gla合成所需的化学功。为什么醌在这个系统中使用时，其他机制存在的CO2固定仍然是神秘的，除非整个过程通过一个电子传递。最终CO2与谷氨酸的γ-亚甲基的加成是否是一个自由基反应还没有定论。由于这种酶是一种内在的膜结合蛋白质，对其结构和功能的科学攻击是目前分子生物学的前沿之一。图9显示了RER中维生素K依赖性蛋白质的合成。最后，人类对维生素K的营养需求尚不清楚。人体中维生素K的一个未知部分来源于肠道植物群中甲基萘醌的生物合成。饮食和生物合成的贡献尚未量化。现在已经有了测量血浆叶绿醌的灵敏HPLC方法，并且可以开发测量长链甲基萘醌的相关方法。
Since the discovery of gamma-carboxyglutamic acid a decade ago, great progress has been made in advancing our knowledge of the function and metabolism of vitamin K. The distribution of this new amino acid in proteins of diverse origin and the presence of the vitamin K-dependent carboxylase in diverse tissues have emphasized the widespread significance in biology of a new triad: vitamin K, Gla, and calcium. New knowledge has been obtained on the importance of the utilization and reutilization of vitamin K, whose body pools are extremely low for a fat-soluble vitamin, for the posttranslational carboxylation of peptide-bound glutamate residues in the vitamin K-dependent proteins. The regulation of the activation of the vitamin K-vitamin K-epoxide cycle by drugs and nutrients appears to be the key to controlling the synthesis of vitamin K-dependent proteins, eight of which are involved in blood coagulation. The purification of the vitamin K-dependent gamma-glutamyl carboxylase has turned out to be a more formidable task than anyone had imagined. Many of the questions about its complicated mechanism, utilizing as it does four substrates (KH2, O2, CO2, and a Glu-containing peptide), cannot be answered until the enzyme is homogeneous. Basically, the vitamin K-dependent carboxylase system consists of a specialized microsomal electron transport system coupled to a carbon dioxide fixation. The reaction does not require ATP but apparently utilizes the energy of vitamin KH2 oxidation to perform the chemical work required in Gla synthesis. Why a quinone is employed in this system when other mechanisms exist for CO2 fixation is still mysterious unless the whole process goes by one electron transport. Whether the final CO2 addition to the gamma-methylene group of glutamic acid is a radical reaction is unsettled. Since this enzyme is an intrinsic membrane-bound protein, the scientific attack on its structure and function is at one of the present frontiers of molecular biology. A view of the synthesis of vitamin K-dependent proteins in the RER is shown in Figure 9. Finally, the nutritional requirements for vitamin K in humans are unknown. An unknown fraction of vitamin K in humans is derived from menaquinone biosynthesis in the intestinal flora. Contributions from diet and biosynthesis have not yet been quantitated. Sensitive HPLC methods for measuring plasma phylloquinone are now available, and related methods for measuring long-chain menaquinones can be developed.