Nonenzymic, polyvalent anion-catalyzed formation of methylglyoxal as an explanation of its presence in physiological systems.

The long standing question of the source of methylglyoxal formed in glycolyzing tissues was considered. Nonbiological studies, made with chemical model systems, made evident that the formation of methylglyoxal from dihydroxyacetone and from Dr.-glyceraldehyde under physiological conditions of pH and temperature is catalyzed by Tris and by certain polyvalent anions including phytate, phosphate, tetraborate, arsenate, arsenite, cacodylate, a,fl-glycerophosphate, glucose B-phosphate, fructose 6-phosphate, and fructose 1,6-diphosphate. Borate and bicarbonate also catalyze the reaction at higher pH values. Methylglyoxal does not accumulate in the presence of other inorganic polyvalent anions, adenosine triphosphate, pyrophosphate, amino acids, polyvalent organic acids, monovalent anions or cations, polyvalent cations, or bovine albumin. The reaction between trioses and phosphate appears to follow second order kinetics. The second order rate constant, kg, is estimated to be 1.2 x 10-Q rn~-'l hr+ for dihydroxyacetone, and 6 X 1O-4 mmP hr-r for glyceraldehyde. The half-life period of the reaction between triose and phosphate ion may be estimated from the equation, tt = lnZ/kz[A], where [A] is the phosphate concentration (mM). The results are considered to be a possible explanation of many published observations of the appearance of methylglyoxal in glycolyzing tissues. The potential for methylglyoxal formation in biological tissues and in certain buffer systems possibly has wide ranging metabolic implications.