Isotope effects as probes for enzyme catalyzed hydrogen-transfer reactions

Kinetic Isotope effects (KIEs) have long served as a probe for the mechanisms of both enzymatic and solution reactions. Here, we discuss various models for the physical sources of KIEs, how experimentalists can use those models to interpret their data, and how the focus of traditional models has grown to a model that includes motion of the enzyme and quantum mechanical nuclear tunneling. We then present two case studies of enzymes, thymidylate synthase and alcohol dehydrogenase, and discuss how KIEs have shed light on the C-H bond cleavages those enzymes catalyze. We will show how the combination of both experimental and computational studies has changed our notion of how these enzymes exert their catalytic powers.