The formation of methylglyoxal from triose phosphates

Abstract

In Krebs-Ringer phosphate buffer, the rate of formation of methylglyoxal from glycerone phosphate and glyceraldehyde 3-phosphate was first order with respect to the triose phosphate with rates constant values of 1.94 2 0.02X10-5 s-' (n = 18) and 1.54 2 0.02X10-4 s-' (n = 18) at 37"C, respectively. The rate of formation of methylglyoxal from glycerone phosphate and glyceraldehyde 3-phosphate in the presence of red blood cell lysate was not significantly different from the nonenzymatic value ( P > 0.05). Methylglyoxal formation from glycerone phosphate was increased in the presence of triose phosphate isomerase but this may be due to the faster non-enzymatic formation from the glyceraldehyde 3-phosphate isomerisation product. For red blood cells in vitro, the predicted non-enzymatic rate of formation of methylglyoxal from glycerone phosphate and glyceraldehyde 3-phosphate may account for the metabolic flux through the glyoxalase system. The reactivity of glycerone phosphate and glyceraldehyde 3-phosphate towards the non-enzymatic formation of methylglyoxal under physiological conditions suggests that methylglyoxal formation is unavoidable from the Embden-Meyerhof pathway.Methylglyoxal (2-oxopropanal) is a metabolite found widespread throughout biological life (Thornalley, 1990 ;Murata et al., 1989;Ohmori et al., 1989;Steinberg and Kaplan, 1984). It was initially thought to be involved in mainstream glycolysis but the discovery of phosphorylated glycolytic intermediates led to its demise as a metabolite of major importance. It has been most widely investigated with respect to the glyoxalase system which catalyses the conversion of methylglyoxal to D-lactate via the intermediate S-(D1actoyl)glutathione (Thornalley, 1990) but it is now receiving renewed interest as a substrate for aldose reductase (Vander Jagt et al., 1992). The toxicity of high doses of methylglyoxal to biological tissue prompted Albert Szent-Gyorgyi to suggest that methylglyoxal was a 'growth-inhibiting factor' or 'retine', and the glyoxalase system a 'growth-promoting factor' or 'promine', and the conflict between these two factors was involved in control of cell growth (Szent-Gyorgyi, 1977). This hypothesis has been superseded by the discovery of oncogenes and peptide factors (Bradshaw and Prentice, 1987), although recent evidence suggests that methylglyoxal, by conversion to S-(D-lactoyl)glutathione, may influence cell Correspondence to P. J. Thornalley,

Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes

“…Increased formation of methylglyoxal arises mainly from increased levels of triosephosphates in cells accumulating high levels of glucose in hyperglycaemia [40][41][42][43]. This is exacerbated by low glyceraldehyde-3-phosphate dehydrogenase activity [37], particularly when inhibited by poly(ADP ribose) polymerase [44].…”

Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products

“…It is a widely occurring compound formed by most glucose-metabolizing cells. MG is formed mainly during the transformation of phosphotriose intermediates along the glycolytic pathway, namely dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (GAP), through a spontaneous non-enzymatic elimination of a phosphate group from the 1,2-enodiolate intermediate form of both phosphotrioses [16]. Methylglyoxal may also be formed in a paracatalytic process, where the enodiol intermediate is decomposed in the catalytic center of triose phosphate isomerase [17].…”

Selective Induction of Heparin-binding Epidermal Growth Factor-like Growth Factor by Methylglyoxal and 3-Deoxyglucosone in Rat Aortic Smooth Muscle Cells

“…Methylglyoxal (2-oxopropanal; MG), 1 a reactive ␣,␤-dicarbonyl metabolite and physiological substrate for the glyoxalase system (1), is formed by the non-enzymatic and enzymatic elimination of phosphate from dihydroxyacetone phosphate, glyceraldehyde-3-phosphate (2,3), and by the oxidation of hydroxyacetone and aminoacetone (4 -6). The estimated rate of formation of methylglyoxal in tissues of normal healthy subjects is approximately 125 M/day which can largely be accounted for as a result of fragmentation of triose phosphates (2).…”

“…The estimated rate of formation of methylglyoxal in tissues of normal healthy subjects is approximately 125 M/day which can largely be accounted for as a result of fragmentation of triose phosphates (2). The glyoxalase system, using reduced glutathione as a cofactor, catalyzes the conversion of methylglyoxal to D-lactate via the intermediate S-D-lactoylglutathione.…”