Inactivation of Muscle Triose Phosphate Isomerase by d- and l-Glycidol Phosphate

Abstract d- and l-glycidol phosphate have been synthesized in order to investigate the stereospecificity of the inactivation of triose phosphate isomerase by glycidol-P. Both enantiomers inactivate the enzyme. Similar concentrations for half-maximal rates of inactivation are found, but maximum Vinact is 10-fold larger for d-glycidol-P than for l-glycidol-P. The same glutamate residue of the protein is esterified by addition to the C1 carbon of both d- and l-glycidol-P. The Vinact difference is explained in terms of the active site stereospecificity. Both isomers show little alkylation rate dependence over the pH range 5.5 to 10. Enolase is also shown to be inactivated by both enantiomers of glycidol-P.