GLYOXALASE-I ENZYME STUDIES .4. GENERAL BASE-CATALYZED ENEDIOL PROTON-TRANSFER REARRANGEMENT OF "METHYL-GLYOXALGLUTATHIONYLHEMITHIOL AND PHENYLGLYOXALGLUTATHIONYLHEMITHIOL ACETAL TO S-LACTOYL-GLUTATHIONE AND S-MANDELOYLGLUTATHIONE FOLLOWED BY HYDROLYSIS - MODEL FOR GLYOXALASE ENZYME-SYSTEM

In the presence of the general bases imidazole and phosphate dianion methyl- and phenylglyoxalglutathionylhemithiol acetals rearrange to the corresponding S-lactoyl-and S-mandeloylglutathiones, respectively, and then hydrolyze to the corresponding acids. NMR-detected incorporation of solvent protons indicates the mechanism of the arrangement to be an enediol proton transfer. The essential catalytic components of the reaction, which with respect to the mechanism is a bona fide model for the enzyme glyoxalase I, are the covalent catalyst glutathione (the coenzyme for the enzymatic process) and a general base. The rate is also enhanced slightly by magnesium ions. The magnitude of the primary kinetic isotope effect for the general base catalyzed reaction is smaller than that for the hydroxide ion (Cannizzaro) catalyzed rearrangement that involves an intramolecular 1, 2-hydride shift mechanism. Reexamination of Franzen—s model reaction using NMR techniques indicates that the N, N-diethylcysteamine catalyzed rearrangement also proceeds via an enediol proton transfer rather than a 1, 2-hydride shift. © 1978, American Chemical Society. All rights reserved.