Garner M M, Burg M B
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Am J Physiol. 1994 Apr;266(4 Pt 1):C877-92. doi: 10.1152/ajpcell.1994.266.4.C877.
The nonideal properties of solutions containing high concentrations of macromolecules can result in enormous increases in the activity of the individual macromolecules. It has been proposed that molecular crowding and confinement occur in cells and are major determinants of the activity of the proteins and other intracellular macromolecules. This concept has important implications for cell volume regulation because, under crowded conditions, relatively small changes in concentration, consequent to alterations of water content, lead to large changes in macromolecular activity. This review considers several aspects of macromolecular crowding and confinement, including: 1) the physical chemical principles involved; 2) in vitro demonstrations of the effects; 3) relation to water activity; 4) estimates of the actual intracellular activity of water and macromolecules; 5) relation to osmotic regulation in various types of cells, including bacteria, red blood cells, and complex nucleated cells; and 6) the relation to inorganic ions and organic osmolytes in cells stressed by hypertonicity. We conclude that, while there is compelling evidence for important effects of molecular crowding in vitro and in red blood cells, the role of macromolecular crowding and confinement in osmotic regulation of more complex cells is an open question that deserves the extensive attention it is currently receiving.
含有高浓度大分子的溶液的非理想性质可能导致单个大分子的活性大幅增加。有人提出，细胞中存在分子拥挤和限制现象，这是蛋白质和其他细胞内大分子活性的主要决定因素。这一概念对细胞体积调节具有重要意义，因为在拥挤条件下，由于含水量的改变而导致的浓度相对较小的变化会引起大分子活性的大幅变化。本综述探讨了大分子拥挤和限制的几个方面，包括：1）所涉及的物理化学原理；2）体外效应的证明；3）与水活性的关系；4）对细胞内水和大分子实际活性的估计；5）与各种类型细胞（包括细菌、红细胞和复杂的有核细胞）的渗透调节的关系；6）与高渗应激细胞中无机离子和有机渗透剂的关系。我们得出的结论是，虽然有令人信服的证据表明分子拥挤在体外和红细胞中具有重要作用，但大分子拥挤和限制在更复杂细胞的渗透调节中的作用仍是一个悬而未决的问题，值得目前正在受到的广泛关注。
