Mechanism for the formation of methylglyoxal from triosephosphates.

Very early in an investigation of the mechanism for the interconversion of dihydroxyacetone phosphate (DHAP) and 1)-glyceraldehyde-3-phosphate (1)GAP) by isomerization I noticed the surprising fact that the isomerization reaction could be detected only against the background of the much faster degradation of these compounds to give methylglyoxal and inorganic phosphate. DHAP and I)GAP are intermediates of glycolysis and, as such, would not be expected to undergo spontaneous degradation to methylglyoxal, a compound that inhibits cellular growth at low concentrations and that is toxic at high concentrations [ 11. Glycolytic enzymes are present at extremely high cellular concentrations to maintain the very large flux of catabolites needed to ‘stoke the cellular engine’. It is difficult to imagine how the spill-off of the toxic byproduct methylglyoxal from this pathway could not have important metabolic consequences, but these have been given relatively little consideration. This paper summarizes investigations of the mechanism for the non-enzymic and triosephosphate-isomerase-catalysed elimination reactions of triosephosphates and the conclusions from this work about the surprising kinetic instability of these compounds. It concludes with a brief commentary on the possible metabolic consequences of these elimination reactions.