METHYLGLYOXAL - FROM A PUTATIVE INTERMEDIATE OF GLUCOSE BREAKDOWN TO ITS ROLE IN UNDERSTANDING THAT EXCESSIVE ATP FORMATION IN CELLS MAY LEAD TO MALIGNANCY

In the 1920s, methylglyoxal, a keto-aldehyde, was widely held as one o f the key intermediates of glucose breakdown. But with the elucidation of Embden-Meyerhof pathway of glycolysis, this idea was rejected. How ever, in the 1970s and the 1980s the metabolic pathway for methylglyox al in different organisms was established. Methylglyoxal has growth-in hibitory and anticancer properties and it had been generally assumed t hat these properties are interrelated. But recent studies have convinc ingly showed that methylglyoxal is tumoricidal. It inhibits mitochondr ial respiration and glycolysis of exclusively malignant cells which cr itically reduces ATP level in these cells rendering them non-viable. W e have obtained strong evidence that in malignant cells both mitochond rial complex I and the glycolytic enzyme glyceraldehyde-3-phosphate de hydrogenase, may be critically altered. Based on these results and con sidering the role of ATP in biological systems, a new hypothesis on ca ncer has been proposed, which suggests that excessive ATP formation in cells may lead to malignancy. Moreover, the reported anticancer prope rty of methylglyoxal strongly suggests that methylglyoxal alone or in combination with some synthetic or natural product(s) should immediate ly be put to trial for the treatment of cancer.