Enzyme chemistry of dithiohemiacetals: synthesis and characterization of S-D-dithiomandeloylglutathione as an alternate substrate for glyoxalase I.
Both the D- and L-forms of S-dithiomandeloylglutathione (1) have been synthesized by a dithioester-interchange reaction between GSH and S-carboxy-methyl(D,L)-dithiomandelate. Kinetic and product analysis studies indicate that yeast glyoxalase I efficiently catalyzes the stereoselective conversion of D-1 to GSH-phenylglyoxal dithiohemiacetal (2), isolated as a disulfide adduct between 2 and a second molecule of GSH. This observation suggests that dithioester substrate analogues should be generally useful as mechanistic probes of enzyme catalyzed reactions involving thiohemiacetal intermediates.
Li
J
J
Department of Chemistry and Biochemistry, University of Maryland Baltimore County 21228.
Guha
M K
MK
Creighton
D J
DJ
D001665:Binding Sites; D002384:Catalysis; D004220:Disulfides / Q000737:chemistry; D005978:Glutathione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D015032:Zinc / Q000378:metabolism
D004220:Disulfides; C072029:S-D-dithiomandeloylglutathione; D007791:Lactoylglutathione Lyase; D005978:Glutathione; D015032:Zinc