Methionine-sensitive glycolysis in transformed cells.
Glycolysis in several tumor cell lines grown in tissue culture was inhibited by methionine. Kirsten murine sarcoma virus-transformed rat kidney cells (K-NRK) were inhibited 60-75% by 10 mM methionine, whereas normal rat kidney (NRK-49F) cells showed little or no inhibition. Inhibition of glycolysis in K-NRK cells was manifest 2-4 hr after exposure to the amino acid. Glycolysis in a chemically transformed cell line of Madin-Darby canine kidney cells was also sensitive to methionine, but maximal inhibition (75%) required 18-24 hr of incubation with the amino acid. Under the same conditions glycolysis in the nontransformed canine cells was less than 20% inhibited by methionine. In Ehrlich ascites tumor cells grown in tissue culture, 10 mM methionine inhibited glycolysis by about 50%. Inhibition of glycolysis, even by 50 mM methionine, was rapidly reversible. Within 2 hr after removal of methionine the rate of glycolytic activity was restored to that observed in control cells. Furthermore, inhibition by methionine required a minimum level (7%) of serum in the growth medium and inhibition was not sensitive to cycloheximide. Only amino acids that are transported by system A (including the nonmetabolized analogue methylaminoisobutyric acid) specifically inhibited glycolysis in tumor cells. The only exception was phenylalanine, which was toxic to both transformed and normal cell lines.
D000596:Amino Acids / Q000494:pharmacology; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007668:Kidney; D007700:Kinetics; D007708:Kirsten murine sarcoma virus / Q000235:genetics*; D008715:Methionine / Q000494:pharmacology*; D051379:Mice; D051381:Rats; D009053:Sarcoma Viruses, Murine / Q000235:genetics*
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D003470:Culture Media; C017911:2-(methylamino)isobutyric acid; D003513:Cycloheximide; D008715:Methionine