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基于能量的葡萄糖通过溶质载体转运蛋白(SLC)进行转运的键合图模型。

Energy-based bond graph models of glucose transport with SLC transporters.

作者信息

Hunter Peter J, Ai Weiwei, Nickerson David P

机构信息

Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.

Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.

出版信息

Biophys J. 2025 Jan 21;124(2):316-335. doi: 10.1016/j.bpj.2024.12.006. Epub 2024 Dec 6.

Abstract

The SLC (solute carrier) superfamily mediates the passive transport of small molecules across apical and basolateral cell membranes in nearly all tissues. In this paper, we employ bond-graph approaches to develop models of SLC transporters that conserve mass, charge, and energy, respectively, and can be parameterized for a specific cell and tissue type for which the experimental kinetic data are available. We show how analytic expressions that preserve thermodynamic consistency can be derived for a representative four- or six-state model, given reasonable assumptions associated with steady-state flux conditions. We present details on fitting parameters for SLC2A2 (a GLUT transporter) and SLC5A1 (an SGLT transporter) to experimental data and show how well the steady-state flux expressions match the full kinetic analysis. Since the bond-graph approach will not be familiar to many readers, we provide a detailed description of the approach and illustrate its application to a number of familiar biophysical processes.

摘要

溶质载体(SLC)超家族介导几乎所有组织中小分子跨顶端和基底外侧细胞膜的被动转运。在本文中,我们采用键图方法来开发SLC转运体模型,这些模型分别守恒质量、电荷和能量,并且可以针对有实验动力学数据的特定细胞和组织类型进行参数化。我们展示了在与稳态通量条件相关的合理假设下,如何为代表性的四态或六态模型推导出保持热力学一致性的解析表达式。我们详细介绍了将SLC2A2(一种葡萄糖转运蛋白)和SLC5A1(一种钠葡萄糖协同转运蛋白)的参数拟合到实验数据的过程,并展示了稳态通量表达式与完整动力学分析的匹配程度。由于许多读者可能不熟悉键图方法,我们对该方法进行了详细描述,并举例说明了其在一些常见生物物理过程中的应用。

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