Evolutionary Aspects of the Oxido-Reductive Network of Methylglyoxal.

In the chemoautotrophic theory for the origin of life, offered as an alternative to broth theory, the archaic reductive citric acid cycle operating without enzymes is in the center. The non-enzymatic (methyl)glyoxalase pathway has been suggested to be the anaplerotic route for the reductive citric acid cycle. In the recent years, much has been learned about methylglyoxal, but its importance in the metabolic machinery is still uncovered. If methylglyoxal had been essential participant of the early stage of evolution, then it is a legitimate question whether it might have played a role in the early oxido-reduction network, too. Therefore, an oxido-reduction network of methylglyoxal that might have functioned under ancient circumstances without enzymes was constructed and analyzed by virtue of group contribution method. Taking methylglyoxal as input material, it turned out that the evolutionary value of reactions and biomolecules were not similar. Glycerol, glycerate, and tartonate, the output components, were conserved to different degrees. Although the tartonate route was similarly favorable from energetic point of view, its intermediates are almost not present in extant biochemistry. The presence of two carboxyl or aldehyde groups, or their combination in tricarbons of the constructed network seemed disadvantageous for selection, and the inductive effect, resulting in an asymmetry in electron cloud of chemicals, might have been important. The evolutionary role for cysteine, H2S, and formaldehyde in the emergence of high-energy bonds in the form of thioesters and in Fe-S cluster formation as well as in imidazole synthesis was shown to bridge the gap between prebiotic chemistry and contemporary biochemistry. Overall, the ideas developed here represent an approach fitting to chemoautotrophic origin of life and implying to the role of methylglyoxal in triose formation. The proposed network is expected to have an impact upon how one may think of prebiological chemical processes on methylglyoxal, too. Finally, along the evolutionary time line, the network functioning without enzymes is situated between the formation of simple organic compounds and primeval cells, being closer to the former and well preceding the last common metabolic ancestor developed after primitive cells emerged.