title: Kinetic isotope effects as a probe of hydrogen transfers to and from common enzymatic cofactors.
abstract: Enzymes use a number of common cofactors as sources of hydrogen to drive biological processes, but the physics of the hydrogen transfers to and from these cofactors is not fully understood. Researchers study the mechanistically important contributions from quantum tunneling and enzyme dynamics and connect those processes to the catalytic power of enzymes that use these cofactors. Here we describe some progress that has been made in studying these reactions, particularly through the use of kinetic isotope effects (KIEs). We first discuss the general theoretical framework necessary to interpret experimental KIEs, and then describe practical uses for KIEs in the context of two case studies. The first example is alcohol dehydrogenase, which uses a nicotinamide cofactor to catalyze a hydride transfer, and the second example is thymidylate synthase, which uses a folate cofactor to catalyze both a hydride and a proton transfer.
authors.affiliation: Department of Chemistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roston
authors.affiliation: Department of Chemistry, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Zahidul
authors.initials: Z
authors.lastname: Islam
authors.affiliation: Department of Chemistry, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: amnon-kohen@uiowa.edu.
authors.forename: Amnon
authors.initials: A
authors.lastname: Kohen
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D003067:Coenzymes / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D009536:Niacinamide / Q000378:metabolism; D013816:Thermodynamics; D013940:Thymidylate Synthase / Q000378:metabolism
chemical_list: D003067:Coenzymes; D009536:Niacinamide; D006859:Hydrogen; D005492:Folic Acid; D000426:Alcohol Dehydrogenase; D013940:Thymidylate Synthase
keywords: Folate; Hydrogen tunneling; Kinetic isotope effects; Marcus-like models; Nicotinamide