Abstract 1487 Enzyme Activation for Hydride Transfer to the NAD Cofactor Pieces

William P. Jencks proposed many years ago that the binding energy from the interaction of enzymes with the nonreacting fragments of many cofactors is utilized to drive exergonic processes that bring about high rates for catalysis at the second reactive cofactor fragment, rather than to cause tight overall binding of the cofactor. We have been working for several years to confirm this hypothesis for enzyme-catalyzed hydride transfer reactions of the nicotinamide adenine dinucleotide (NAD) cofactor.