Methylglyoxal and glucose metabolism: a historical perspective and future avenues for research.

Methylglyoxal, an alpha-oxoaldehyde discovered in the 1880s, has had a hectic scientific career, at times being considered of fundamental importance and at other times viewed as playing a very subordinate role. Much has been learned about methylglyoxal, but the function of its production in the metabolic machinery is still unknown. This paper gives an overview of the changing role of methylglyoxal from a historical aspect and arrives at the conclusion that methylglyoxal is tightly bound to glycolysis from an evolutionary perspective, its production therefore being inevitable. It is not situated in the main stream of the glycolytic sequence, but a role can be assigned to its production in the phosphate supply of operating glycolysis in some prokaryotes and yeast under conditions of phosphate deficiency. This function is presumed to be performed by the enzyme methylglyoxal synthase, which is specialized for the conversion of dihydroxyacetone-phosphate to methylglyoxal. However, it is still unknown whether this enzyme and this kind of regulation also exist in animals.