PHYSICOCHEMICAL STUDIES OF BIOCHEMICAL REACTIONS

该项目的总体目标是应用物理化学技术和 各种生化和生物过程的原理。 尽管我们将一如既往地继续努力，以 测定和解释这类过程的热力学， 人们经常发现，重要的非热力学结果是 获得。我们的研究可以通过下面的例子来说明。(A) 差示扫描量热法(DSC)为研究 大范围物质与脂类相互作用的研究 双层悬浮液作为生物膜的模型。我们是 用差示扫描量热法研究对小分子脂双层的影响 包括各种类型的药物和蛋白质。(B)最近的发展 表明对蛋白质变性进行仔细的DSC研究可以给出 关于蛋白质结构的重要信息，特别是 将这些结构划分为或多或少独立的领域。 (C)等温量热法是测定的最佳方法 在生化过程中的热容和热容的变化。我们 最近在研究FMN与FMN的结合时使用了这项技术 磷酸化酶a和葡萄糖转化为己糖激酶。(D)我们已证明 DSC在细胞过程的研究中可能非常有用，比如 作为吞噬作用，不仅用于评价人体的能量 这不仅有助于对所涉机制有新的认识，而且也有助于对这一过程有新的认识。

The general aim in this project is to apply physicochemical techniques and principles to a wide variety of biochemical and biological processes. Although our efforts will continue, as in the past, to be centered on the determination and interpretation of the thermodynamics of such processes, it is frequently found that significant non-thermodynamic results are obtained. Our research may be illustrated by the following examples. (a) Differential scanning calorimetry (DSC) affords a powerful tool for the study of the interactions of a broad range of substance with lipids in bilayer suspension serving as models for biological membranes. We are using DSC to investigate the effects on lipid bilayers of small molecules including drugs of various types, and of proteins. (b) Recent developments indicate that careful DSC studies of protein denaturation can give important information concerning the structures of proteins, in particular the division of these structures into more or less independent domains. (c) Isothermal calorimetry provides the best method for the determination of the enthalpy and heat capacity changes in biochemical processes. We have recently used this technique in studies of the binding of FMN to phosphorylase a and of glucose to hexokinase. (d) We have demonstrated that DSC is potentially very useful in the study of cellular processes such as phagocytosis, not only for the evaluation of the energetics of the process but also in obtaining new insights into the mechanisms involved.