Biomaterial Database

The role of zinc-bound water in liver alcohol dehydrogenase catalysis. 1980

S A Evans, and J D Shore

To elucidate the role of zinc-bound water in liver alcohol dehydrogenase catalysis, chelation by 1,10-phenanthroline and 2,2-bipyridine was studied. The rate constants for association of both chelating agents to the active center zinc were pH-dependent with a pKa of 9.2 and preferential binding to a protonated form. The binary complex dissociation rate constants were pH-independent for both chelating agents. In the presence of saturating NAD+, the pKa for the equilibrium binding of 2,2-bipyridine was perturbed to 7.6, similar to the functional group previously shown to be involved in NAD+ binding. The presence of saturating imidazole resulted in pH-independent 2,2-bipyridine binding. These studies provide compelling evidence that the ionizing enzyme functional group involved in coenzyme binding, proton liberation, and conformational states is zinc-bound water. The limiting rate of chelation by 2,2-bipyridine was pH-independent, and no limiting rate was observed in the presence of saturating imidazole. These results indicate that the limiting rate of chelation is due to the rate of dissociation of zinc-bound water. The implications of this regarding the role of zinc in catalytic turnover of liver alcohol dehydrogenase are discussed.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D010618	Phenanthrolines		Phenanthroline
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D006736	Horses	Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest.	Equus caballus,Equus przewalskii,Horse, Domestic,Domestic Horse,Domestic Horses,Horse,Horses, Domestic
D006860	Hydrogen Bonding	A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.	Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D000429	Alcohol Oxidoreductases	A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).	Carbonyl Reductase,Ketone Reductase,Carbonyl Reductases,Ketone Reductases,Oxidoreductases, Alcohol,Reductase, Carbonyl,Reductase, Ketone,Reductases, Carbonyl,Reductases, Ketone
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D014867	Water	A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Hydrogen Oxide