Hernández J A, Fischbarg J
Departamento de Biofísica y Bioquímica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Biophys J. 1994 Sep;67(3):996-1006. doi: 10.1016/S0006-3495(94)80565-X.
Complex facilitative membrane transporters of specific ligands may operate via inner channels subject to conformational transitions. To describe some properties of these systems, we introduce here a kinetic model of coupled transport of two species, L and w, through a two-conformational pore. The basic assumptions of the model are: a) single-file of, at most, n molecules inside the channel; b) each pore state is open to one of the compartments only; c) there is at most only one vacancy per pore; d) inside the channel, a molecule of L occupies the same positions as a molecule of w; and e) there is at most only one molecule of L per pore. We develop a general representation of the kinetic diagram of the model that is formally similar to the one used to describe one-vacancy transport through a one-conformational single-file pore. In many cases of biological importance, L could be a hydrophilic (ionic or nonionic) ligand and w could be water. The model also finds application to describe solute (w) transport under saturation conditions. In this latter case, L would be another solute, or a tracer of w. We derive steady-state expressions for the fluxes of L and w, and for the permeability coefficients. The main results obtained from the analysis of the model are the following. 1) Under the condition of equilibrium of w, the expression derived for the flux of L is formally indistinguishable from the one obtainable from a standard four-state model of ligand transport mediated by a two-conformational transporter. 2) When L is a tracer of w, we can derive an expression for the ratio between the main isotope and tracer permeability coefficients (Pw/Pd). We find that the near-equilibrium permeability ratio satisfies (n - 1) < or = (Pw/Pd)eq < or = n, a result previously derived for the one-conformational, single-file pore for the case that n > or = 2. 3) The kinetic model studied here represents a generalization of the carrier concept. In fact, for the case that n = 1 (corresponding to the classical single-occupancy carrier), the near-equilibrium permeability ratio satisfies 0 < or = (Pw/Pd)eq < or = 1, which is characteristic of a carrier performing exchange-diffusion.
特定配体的复杂易化膜转运体可能通过经历构象转变的内部通道发挥作用。为了描述这些系统的一些特性，我们在此引入一种动力学模型，用于描述两种物质L和w通过双构象孔的耦合转运。该模型的基本假设如下：a）通道内分子最多以单列形式排列，数量为n；b）每个孔状态仅对其中一个隔室开放；c）每个孔最多只有一个空位；d）在通道内，一个L分子占据的位置与一个w分子相同；e）每个孔最多只有一个L分子。我们构建了该模型动力学图的一般表示形式，它在形式上类似于用于描述通过单构象单列孔的单空位转运的动力学图。在许多具有生物学重要性的情况下，L可以是亲水性（离子性或非离子性）配体，而w可以是水。该模型还可用于描述饱和条件下溶质（w）的转运。在后一种情况下，L将是另一种溶质，或w的示踪剂。我们推导了L和w通量以及渗透系数的稳态表达式。对该模型分析得出的主要结果如下。1）在w平衡的条件下，推导得到的L通量表达式在形式上与通过双构象转运体介导的配体转运的标准四态模型得到的表达式无法区分。2）当L是w的示踪剂时，我们可以推导主同位素与示踪剂渗透系数之比（Pw/Pd）的表达式。我们发现近平衡渗透比满足（n - 1）≤（Pw/Pd）eq≤n，这一结果先前在n≥2的情况下针对单构象单列孔推导得出。3）此处研究的动力学模型代表了载体概念的一种推广。实际上，对于n = 1的情况（对应于经典的单占据载体），近平衡渗透比满足0≤（Pw/Pd）eq≤1，这是进行交换扩散的载体的特征。
