Caution: the glycylmethyl and glycylethyl esters of glutathione are substrates for glyoxalase I.
The glycylmethyl and glycylethyl esters of glutathione have been synthesized and carefully characterized by both 1H-NMR and tandem FAB mass spectrometry. Contrary to previously published studies, these compounds (as their methylglyoxal-thiohemiacetals) do indeed serve as moderately efficient substrates for yeast glyoxalase I, with kcat values that are approx. 3-fold smaller and Km values that are approx. 3-fold larger than those of the thiohemiacetal formed from glutathione. Product inhibition studies show that the glycylmethyl and glycylethyl esters of (S)-D-lactoylglutathione bind approx. 1.4-fold less tightly to the active site than (S)-D-lactoylglutathione. These observations exclude an essential role for the glycyl-CO2- of substrate in active site binding and catalysis.
Hamilton
D S
DS
Department of Chemistry and Biochemistry, University of Maryland Baltimore County, MD 21228.
Creighton
D J
DJ
D000595:Amino Acid Sequence; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013379:Substrate Specificity
C077304:glutathione glycylethyl ester; C077303:glutathione glycylmethyl ester; D007791:Lactoylglutathione Lyase; D005978:Glutathione