Methylglyoxal in living organisms: chemistry, biochemistry, toxicology and biological implications

Despite the growing interest towards methylglyoxal and glyoxalases their real role in metabolic network is still obscure. In the light of developments several reviews have been published in this field mainly dealing with only a narrow segment of this research area. In this article a trial is made to present a comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methylglyoxal metabolism and toxicity in a wide variety of species, and emphasizing the action of methylglyoxal on energy production, free radical generation and cell killing. Special attention is paid to the discussion of alpha-oxoaldehyde production in the environment as a potential risk factor and to the possible role of this a-dicarbonyl in diseases. Concerning the interaction of methylglyoxal with biological macromolecules (DNA, RNA, proteins) an earlier review (Kalapos, Toxicology Letters, 73, 1994, 3-24) means a supplementation to this paper, thus hoping the avoidance of unnecessary bombast. The paper arrives at the conclusion that since the early stage of evolution the function of methylglyoxalase pathway has been related to carbohydrate metabolism, but its significance has been changed over the thousands of years. Namely, at the beginning of evolution methylglyoxalase path was essential for the reductive citric acid cycle as an anaplerotic route, while in the extant metabolism it concerns with the detoxification of methylglyoxal and plays some regulatory role in triose-phosphate household. As there is a tight junction between methylglyoxal and carbohydrate metabolism its pathological role in the events of the development of diabetic complications emerges in a natural manner and further progress is hoped in this field. In contrast, significant advancement cannot be expected in relation to cancer research.