The proposed research seeks to establish pressure effects on enzyme kinetics as a diagnostic of enzyme mechanism of the same sort as initial rate kinetic studies at constant pressure have been for the last 40 years or so. Pressure effect studies on formate dehydrogenase will be correlated with isotope effect studies. The pressure effect kinetic expressions will be developed and compared with the results obtained with a series of enzymes whose catalytic mechanisms are presumed to be known. %%% Studies of the time-dependence of enzyme-catalyzed reactions as a function of enzyme, substrate, and inhibitor concentration have developed into a paradigm for characterizing catalytic mechanism (ie. the timing of bond-making and bond-breaking events during the converstion of substrate into products). Understanding of enzyme mechanism is important for developemnt of better substrates or inhibitors, etc. Mechanism information is useful for understanding how metabolism works and for the design of drugs and enzyme assays. The study of pressure effects on enzyme catalysis has the potential of developing into another powerful diagnostic of mechanism which is both independent of and complementary to concentration- dependence studies. The proposed work could provide revolutionary new insights into enzyme function studies.
