1B93

Methylglyoxyl synthase catalyses the first reaction in the methylglyoxyl bypass of the Embden-Myerhoff pathway (glycolysis), the conversion of dihydroxyacetone phosphate into methylglyoxal and orthophosphate. The physiological benefits of this are yet to be understood as the final product of methylglyoxal synthase is cytotoxic in small quantities and has been shown to be mutagenic and to interfere with de novo protein and nucleic acid synthesis. The intermediate, D-lactoylglutathione is also toxic in millimolar quantities, interfering with intermediate filament synthesis. The methylglyoxyl bypass system is inhibited allosterically by phosphate suggesting that is only functions in times of phosphate deprivation although more recent data imply that it may facilitate the transition between conditions of high and low phosphate. There is much interest in this enzyme for two reasons: firstly it has been implicated in diabetic complications and secondly due to its ability to metabolise anti-cancer drugs rendering treatments ineffective.