PHYSICOCHEMICAL STUDIES OF BIOCHEMICAL REACTIONS

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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.