Centre for Haemostasis and Thrombosis, Guy's and St Thomas' NHS Foundation Trust, London SE1 7EH, United Kingdom; email:
Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe 658-8558 Japan; email:
Annu Rev Nutr. 2018 Aug 21;38:127-151. doi: 10.1146/annurev-nutr-082117-051741. Epub 2018 Jun 1.
Vitamin K (VK) is an essential cofactor for the post-translational conversion of peptide-bound glutamate to γ-carboxyglutamate. The resultant vitamin K-dependent proteins are known or postulated to possess a variety of biological functions, chiefly in the maintenance of hemostasis. The vitamin K cycle is a cellular pathway that drives γ-carboxylation and recycling of VK via γ-carboxyglutamyl carboxylase (GGCX) and vitamin K epoxide reductase (VKOR), respectively. In this review, we show how novel molecular biological approaches are providing new insights into the pathophysiological mechanisms caused by rare mutations of both GGCX and VKOR. We also discuss how other protein regulators influence the intermediary metabolism of VK, first through intestinal absorption and second through a pathway that converts some dietary phylloquinone to menadione, which is prenylated to menaquinone-4 (MK-4) in target tissues by UBIAD1. The contribution of MK-4 synthesis to VK functions is yet to be revealed.
维生素 K（VK）是一种必需的辅因子，用于将肽结合的谷氨酸进行翻译后转化为γ-羧基谷氨酸。由此产生的依赖维生素 K 的蛋白质被认为具有多种生物学功能，主要用于维持止血。维生素 K 循环是一种细胞途径，通过γ-羧基谷氨酸羧化酶（GGCX）和维生素 K 环氧化物还原酶（VKOR）分别驱动 VK 的γ-羧化和循环利用。在这篇综述中，我们展示了新的分子生物学方法如何为 GGCX 和 VKOR 两种罕见突变引起的病理生理机制提供新的见解。我们还讨论了其他蛋白质调节剂如何通过肠道吸收和将部分膳食叶绿醌转化为甲萘醌的途径来影响 VK 的中间代谢，甲萘醌在靶组织中由 UBIAD1 异戊二烯化为甲萘醌-4（MK-4）。MK-4 合成对 VK 功能的贡献尚待揭示。
