Enzymes are the catalysts that control virtually all chemical reactions in living systems. The mechanisms by which these catalysts work and are controlled continues to be an important objective of biological studies, with implications for drug design regulation of biological processes, and other areas. The goal of this work is to determine in detail the mechanisms by which enzymes function. The principal technique being applied is heavy-atom isotope effects which can provide a number of important details of mechanism, including order of addition of various substrates to the enzyme, relative rates of various steps, nature of various intermediates and transition states, and the role of various enzyme functional groups in the overall catalytic process. Enzymes being studied include aspartate transcarbamylase, glutamine synthetase, and phosphoenolpyruvate carboxykinase. Model studies will provide important reference points for interpreting the results of these studies.
