SIMILAR NATURE OF INHIBITION OF MITOCHONDRIAL RESPIRATION OF HEART-TISSUE AND MALIGNANT-CELLS BY METHYLGLYOXAL - A VITAL CLUE TO UNDERSTANDTHE BIOCHEMICAL BASIS OF MALIGNANCY

The effect of methylglyoxal on the oxygen consumption of mitochondria of heart and of several other organs of normal animals of different sp ecies has been rested. The results indicate that methylglyoxal (3.5 mM ) strongly inhibits ADP-stimulated alpha-oxoglutarate and malate plus pyruvate-dependent respiration of exclusively heart mitochondria of no rmal animals of different species. Whereas, with the same substrates, but at a higher concentration of methylglyoxal (7.5 mM), the respirati on of mitochondria of other organs of normal animals is not inhibited. Methylglyoxal also inhibits the respiration of slices of rat and toad hearts. But this inhibition is less pronounced. However, methylglyoxa l (15 mM) fails to have any effect on perfused toad heart. Using rat h eart mitochondria as a model, the effect of methylglyoxal on the oxyge n consumption was also tested with different respiratory substrates, e lectron donors al different segments of the mitochondrial respiratory chain and site-specific inhibitors to identify the specific respirator y complex which might be involved in the inhibitory effect of methylgl yoxal. The results strongly suggest that methylglyoxal inhibits the el ectron flow through complex I of rat heart mitochondrial respiratory c hain. Moreover, lactaldehyde (0.6 mM), a catabolite of methylglyoxal, can exert a protective effect on the inhibition of rat heart mitochond rial respiration by methylglyoxal (2.5 mM). The effect of methylglyoxa l on heart mitochondria as described in the present paper is strikingl y similar to the results of our previous work with mitochondria of Ehr lich ascites carcinoma cells and leukemic leukocytes. We have recently proposed a new hypothesis on cancer which suggests that excessive ATP formation in cells may lead to malignancy. The above mentioned simila rity apparently provides a solid experimental foundation for the propo sed hypothesis which has been discussed.