The effects of some analogues of glutathione on the glyoxalase system

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Abstract
Some glutathione (GSH) analogues were tested on the complete glyoxalase system (glyoxalase I plus glyoxalase II) and shown to be inhibitory. No quantitative deductions could be made because of the complexity of the system. The non-enzymic reaction between GSH and methylglyoxal in aqueous solution involved a small increase in optical density which could be used to follow the reaction. The equilibrium constant was approximately 10-2.3 [image]. The variation in the velocity of the enzymic reaction with GSH concentration was studied at 2 different concentrations of methylglyoxal. The results suggest that the enzyme combines with free GSH and not with the GSH combined with methylglyoxal in the non-enzymic reaction; the Michaelis constant for the equilibrium is 0.46 x 10-3[image]. The effect of analogues of GSH on the glyoxalase I reaction was studied and some were inhibitory. The stability constants of the enzyme-inhibitor complexes (Ki) were calculated and the nature of the inhibition investigated. The relationship between the structure of the analogues and the degree and type of inhibition they produced is discussed in the light of the mathematical theory of enzyme inhibition briefly outlined. A non-enzymic reaction of L-cysteine and of L-cysteinylglycine with methylglyoxal caused a large increase in optical density. It differed from the reaction of GSH and methylglyoxal and probably involved the formation of a thiazolidine ring.