Methylglyoxal: From a putative intermediate of glucose breakdown to its role in understanding that excessive ATP formation in cells may lead to malignancy [Review]

摘要

In the 1920s, methylglyoxal, a keto-aldehyde, was widely held as one of the key intermediates of glucose breakdown. But with the elucidation of Embden-Meyerhof pathway of glycolysis, this idea was rejected. However, in the 1970s and the 1980s the metabolic pathway for methylglyoxal in different organisms was established. Methylglyoxal has growth-inhibitory and anticancer properties and it had been generally assumed that these properties are interrelated. But recent studies have convincingly showed that methylglyoxal is tumoricidal. It inhibits mitochondrial respiration and glycolysis of exclusively malignant cells which critically reduces ATP level in these cells rendering them non-viable. We have obtained strong evidence that in malignant cells both mitochondrial complex I and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, may be critically altered. Based on these results and considering the role of ATP in biological systems, a new hypothesis on cancer has been proposed, which suggests that excessive ATP formation in cells may lead to malignancy. Moreover, the reported anticancer property of methylglyoxal strongly suggests that methylglyoxal alone or in combination with some synthetic or natural product(s) should immediately be put to trial for the treatment of cancer. [References: 110]