Hernández J A, Fischbarg J, Vera J C
Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
J Membr Biol. 1996 Jan;149(1):57-69. doi: 10.1007/s002329900007.
The four-state simple carrier model (SCM) is employed to describe ligand translocation by diverse passive membrane transporters. However, its application to systems like facilitative sugar transporters (GLUTs) is controversial: unidirectional fluxes under zero-trans and equilibrium-exchange experimental conditions fit a SCM, but flux data from infinite-cis and infinite-trans experiments appear not to fit the same SCM. More complex kinetic models have been proposed to explain this "anomalous" behavior of GLUTs, but none of them accounts for all the experimental findings. We propose an alternative model in which GLUTs are channels subject to conformational transitions, and further assume that the results from zero-trans and equilibrium-exchange experiments as well as trans-effects corresponds to a single-occupancy channel regime, whereas the results from the infinite-cis and infinite-trans experiments correspond to a regime including higher channel occupancies. We test the plausibility of this hypothesis by studying a kinetic model of a two-site channel with two conformational states. In each state, the channel can bind the ligand from only one of the compartments. Under single-occupancy, for conditions corresponding to zero-trans and equilibrium-exchange experiments, the model behaves as a SCM capable of exhibiting trans-stimulations. For a regime including higher degrees of occupancy and infinite-cis and infinite-trans conditions, the same channel model can exhibit a behavior qualitatively similar to a SCM, albeit with kinetic parameters different from those for the single-occupancy regime. Numerical results obtained with our model are consistent with available experimental data on facilitative glucose transport across erythrocyte membranes. Hence, if GLUTs are multiconformational channels, their particular kinetic properties can result from transitions between single and double channel occupancies.
四态简单载体模型（SCM）被用于描述多种被动膜转运蛋白介导的配体转运。然而，将其应用于易化性糖转运蛋白（GLUTs）等系统存在争议：零转运和平衡交换实验条件下的单向通量符合SCM，但无限顺式和无限反式实验的通量数据似乎不符合同一SCM。人们提出了更复杂的动力学模型来解释GLUTs的这种“异常”行为，但没有一个模型能解释所有实验结果。我们提出了一种替代模型，其中GLUTs是经历构象转变的通道，并进一步假设零转运和平衡交换实验的结果以及转运效应对应于单占据通道状态，而无限顺式和无限反式实验的结果对应于包含更高通道占据率的状态。我们通过研究具有两种构象状态的双位点通道的动力学模型来检验这一假设的合理性。在每种状态下，通道只能从一个隔室结合配体。在单占据情况下，对于对应于零转运和平衡交换实验的条件，该模型表现为能够展现转运刺激的SCM。对于包含更高占据度以及无限顺式和无限反式条件的状态，相同的通道模型可以展现出与SCM定性相似的行为，尽管其动力学参数与单占据状态不同。我们模型得到的数值结果与关于葡萄糖跨红细胞膜易化转运的现有实验数据一致。因此，如果GLUTs是多构象通道，它们独特的动力学特性可能源于单通道和双通道占据之间的转变。
