The inhibitory effect of L-cysteine and its derivatives on glycolysis in Ehrlich ascites tumour cells.

L-Cysteine inhibits aerobic glycolysis and restores the Pasteur effect in Ehrlich ascites tumour cells or in their supernatants, while D-cysteine has no effect on this process. Other compounds which have configuration L at the alpha-carbon and a thiol group in the beta-position (penicillamine) or restore them in vivo (3-mercaptopyruvate, cystine or L-serine together with L-homocysteine) also show inhibitory properties. DL-Homocysteine with a free thiol group in the gamma-position, reduced glutathione, methionine and products of cysteine oxidation (cysteic acid, taurine) do not inhibit tumour aerobic glycolysis. Glycolysis of normal tissue supernatants (mouse liver and muscle) is not sensitive to the inhibitory effect of cysteine. Metabolic studies showing a cysteine-induced decrease in ATP content, coupled with cross-over of the pyruvate and 2-phosphoenolpyruvate concentrations in Ehrlich ascites tumour cells, indicate that tumour pyruvate kinase is an enzyme sensitive to cysteine inhibition. Enzymatic studies carried out both after preincubation of Ehrlich ascites tumour cells with cysteine or during direct action of this substance on tumour and normal tissue supernatants indicate the presence of a cysteine-sensitive isoenzyme besides the normal cysteine-insensitive pyruvate kinase in tumour material.