Cai Z S, Burczynski F J, Luxon B A, Forker E L
Department of Medicine, University of Missouri-Columbia 65212.
Am J Physiol. 1992 Jun;262(6 Pt 1):G1127-37. doi: 10.1152/ajpgi.1992.262.6.G1127.
The liver's apparently anomalous extraction of organic anions tightly bound to albumin continues to provoke controversy and confusion. Decisive experiments have proved difficult to design, and mathematical models have usually been constructed to defend one or another putative mechanism to the exclusion of others. To stimulate more decisive experiments and as an aid to interpreting those already reported, we discuss a general formulation of the problem that predicts the clearance pattern to be expected when facilitated dissociation and codiffusion are joint determinants of the uptake flux. The results provide an approach to modeling the various mechanisms by which the concentration of bound ligand at the cell surface could be a driving force for uptake. Further we present new calculations to clarify the interpretation of net ligand clearance when the removal of free ligand is the result of bidirectional fluxes into and out of an unstirred sink. Applied to a previously published comparison of the uptake performances of hepatocytes and polyethylene, the new calculations support the inference that facilitated dissociation of albumin-palmitate complexes occurs at or near the hepatocyte surface.
肝脏对紧密结合白蛋白的有机阴离子的明显异常摄取，持续引发争议和困惑。设计决定性实验已证明困难重重，数学模型通常是为捍卫某一种或另一种假定机制而构建，从而排斥了其他机制。为推动更多决定性实验，并辅助解读已报道的实验，我们讨论了该问题的一般表述，它预测了促进解离和协同扩散共同决定摄取通量时预期的清除模式。这些结果提供了一种对各种机制进行建模的方法，通过这些机制，细胞表面结合配体的浓度可以成为摄取的驱动力。此外，我们给出了新的计算结果，以阐明当游离配体的清除是由于进出未搅拌池的双向通量导致时，对净配体清除的解释。应用于先前发表的肝细胞和聚乙烯摄取性能的比较，新的计算结果支持了这样的推断：白蛋白 - 棕榈酸酯复合物的促进解离发生在肝细胞表面或其附近。
