Metabolism of neoplastic tissue. XIV. Methylglyoxal formation during glucose catabolism in tumors.

The wide distribution of glyoxalase in cells (5, 6, 7, 15, 17) has drawn attention to the possible role of methylglyoxal as an intermediate of carbohydrate breakdown, and the high aerobic and anaerobic glycolysis of tumor cells has suggested a possible special significance of this substance in tumor metabolism. However, the lack of any striking differences from non-neoplastic tissues in the activity of glyoxalase of tumors has discounted such a possibility. At present, the principal arguments against methylglyoxal as a biological precursor of lactic acid rest on the observations (a) that the product of glyoxalase action is D-lactic acid (5), whereas the L-isomer is produced by both neoplastic and non-neoplastic cells (3); and (b) methylglyoxal can be formed nonenzymatically from hexose diphosphate, glyceraldehyde, and glyceraldehyde-3-phosphate (1s 13). However, the participation of methylglyoxal has not been completely disproved, and the possibility of its role in glucose breakdown in leukocytes has been reopened recently by results of McKinney and his associates (8, 10, 11). McKinney and Rundles (11) reported a relationship between glyoxalase activity and glycolytic activity in normal and leukemic leukocytes, and McKinney and Martin (10) found that normal leukocytes produce lactic acid in the presence of inhibitors of certain enzymes of the classical Embden-Meyerhof pathway. This group has concluded that not all the lactate produced by leukocytes could have been derived from pyruvate. As part of a program of study of the factors responsible for the high glycolysis of tumors, the participation of methylglyoxal was evaluated with the use of an isotope "trapping" procedure. Various tumor preparations were incubated with glucose uniformly labeled with carbon-14, together