Mechanism of action of vitamin K: synthesis of gamma-carboxyglutamic acid.
Mechanism of action of vitamin K: synthesis of gamma-carboxyglutamic acid.
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维生素K的作用机制：γ-羧基谷氨酸的合成。
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发表时间：
1980
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影响因子：
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通讯作者：
J. Suttie
中科院分区：
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作者：
J. Suttie
维生素K（2-甲基-3-植基-1，4-萘醌）是合成凝血酶原、因子VII、因子IX、因子X和许多新发现的蛋白质所必需的。这些血浆蛋白参与钙依赖性磷脂膜相互作用，该相互作用通过其氨基末端区域存在的γ-羧基谷氨酰残基介导。维生素K是将这些蛋白质的肝前体中的谷氨酰残基转化为完整血浆蛋白中的γ-羧基谷氨酰残基所必需的。在缺乏维生素K或存在维生素K拮抗剂的情况下，动物产生缺乏羧化残基的血浆形式。这些蛋白质是无功能的，因为它们缺乏磷脂相互作用。已在大鼠肝微粒体制剂中研究了进行该反应的维生素K依赖性羧化酶，该酶将羧化内源性前体蛋白。与凝血酶原前体区域同源的低分子量含谷氨酰的肽底物，如Phe-Leu-Glu-Glu-Leu，也将用作洗涤剂溶解的酶的底物。这种酶已被证明需要还原形式的维生素和O2，但不需要ATP或含生物素的蛋白质来维持其活性。同样的微粒体制剂也会将维生素K转化为其2，3-环氧化物，这种活性可能与维生素在驱动羧化酶反应中的作用有关。
Vitamin K (2-methyl-3-phytyl-1,4-naphthoquinone) is required for the synthesis of prothrombin, Factor VII, Factor IX, Factor X, and a number of newly discovered proteins. These plasma proteins participate in calcium-dependent phospholipid membrane interactions which are mediated through the presence of gamma-carboxyglutamyl residues in their amino-terminal region. Vitamin K is required for the postribosomal conversion of glutamyl residues in liver precursors of these proteins to gamma-carboxyglutamyl residues in the completed plasma proteins. In the absence of vitamin K, or in the presence of vitamin K antagonists, animals produce plasma forms which lack the carboxylated residue. These proteins are nonfunctional because of their lack of phospholipid interaction. The vitamin K-dependent carboxylase which carries out this reaction has been studied in rat liver microsomal preparations where it will carboxylate the endogenous precursor proteins. Low-molecular-weight glutamyl-containing peptide substrates, such as Phe-Leu-Glu-Glu-Leu, which are homologous to regions of the prothrombin precursor, will also serve as substrates for the detergent-solubilized enzyme. This enzyme has been shown to require the reduced form of the vitamin and O2 but no ATP or a biotin-containing protein for its activity. The same microsomal preparations will also convert vitamin K to its 2,3-epoxide, and it is possible that activity may be related to the role of the vitamin in driving the carboxylase reaction.