The Dynamics of the Colloidal Interplay of Bile and Vitamin K1

Lena Scheller, Mara Ludescher, Malte Mildner, Theresa Zorn, Simon Hanio, Susanne Morgenroth, Tessa Lühmann, Ann-Christin Pöppler* and Lorenz Meinel*, 
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Abstract

Vitamin K1 is an essential cofactor for the posttranslational modification of Vitamin K1-dependent proteins, regulating blood coagulation, bone mineralization, and anti-inflammatory processes. Its bile-dependent bioavailability points toward the importance of understanding its largely unknown interplay with bile. We detailed the interaction of Vitamin K1 with bile using simulating intestinal fluids and studied the effects of bile on Vitamin K1 solubilization and permeation across artificial membranes. Our results indicate that transitioning from fasted to the fed-state bile concentrations critically impacted Vitamin K1 performances. In the fasted state, flux inversely correlated with the bile concentrations. Starting at the fasted-to-fed transition, this flipped, and Vitamin K1 solubility increased 8-fold, while the flux increased up to 5-fold. When fed, Vitamin K1 was mainly present in small colloidal species, maintaining Vitamin K1 solubility and rapid exchange dynamics with the surrounding fluids. In conclusion, a fed state is a critical prerequisite for effective Vitamin K1 solubilization and molecular presentation within the gastrointestinal tract. Analogous studies with Vitamin D3, another lipophilic vitamin, provided evidence that the mechanism of bile interaction now detailed for Vitamin K1 is not conserved across different vitamins. These outcomes detail Nature’s strategy for the nutritional exploitation of Vitamin K1 by bile, with immediate relevance for diet plans and future nutraceutical designs.

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胆汁和维生素K1胶体相互作用的动力学
维生素K1是维生素K1依赖蛋白翻译后修饰的重要辅助因子,调节血液凝固、骨矿化和抗炎过程。其依赖胆汁的生物利用度指出了了解其与胆汁的相互作用的重要性。我们通过模拟肠液详细研究了维生素K1与胆汁的相互作用,并研究了胆汁对维生素K1增溶和通过人工膜渗透的影响。我们的研究结果表明,从禁食状态过渡到进食状态的胆汁浓度严重影响了维生素K1的性能。在禁食状态下,通量与胆汁浓度呈负相关。从速食过渡开始,这种情况发生了逆转,维生素K1的溶解度增加了8倍,而通量增加了5倍。饲喂时,维生素K1主要存在于小的胶体中,维持了维生素K1的溶解度和与周围液体的快速交换动力学。综上所述,饲喂状态是维生素K1有效溶解和分子在胃肠道内呈现的关键先决条件。对另一种亲脂性维生素维生素D3的类似研究提供了证据,表明现在详细描述的维生素K1的胆汁相互作用机制在不同的维生素中并不保守。这些结果详细说明了大自然通过胆汁对维生素K1进行营养利用的策略,与饮食计划和未来的营养保健设计直接相关。
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