Effect of methionine deprivation on S-adenosylmethionine decarboxylase of tumour cells.
Transference of Walker carcinoma and TLX5 lymphoma from normal L-methionine-containing medium to medium containing limiting amounts of L-methionine, or L-homocysteine only, caused a 2-fold increase of S-adenosylmethionine decarboxylase activity. Kinetic analysis showed an increase in the V value of the enzyme from 22 to 53 pmol/min per mg protein in media containing only 0.1 mM L-homocysteine, without any alteration in the Km value (0.1 mM). The increase in enzyme activity does not result from (a) a reduction of the intracellular level of S-adenosylmethionine, since cycloleucine, an inhibitor of methionine adenosyltransferase, had no effect on enzyme activity; (b) an increase in intracellular adenosine 3',5' monophosphate (cyclic AMP), since high extracellular concentrations of N6-monobutyryl cyclic AMP had no effect on enzyme activity; (c) an alteration of polyamine levels, since addition of micromolar concentrations of exogenous putrescine, spermidine and spermine did not prevent the induction of S-adenosylmethionine decarboxylase activity in methionine-free media containing 0.1 mM L-homocysteine. The increased enzyme activity appears to be mainly due to enhanced stabilization, since the half-life was increased from 2.45 to 5.0 h in media containing only 0.1 mM L-homocysteine. Induction of enzyme activity is specific to the removal of L-methionine, since no increase occurred in the absence of L-serine or L-glycine, or both, or by reduction of the serum concentrations in the medium.
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000031:analogs & derivatives / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000378:metabolism*; D002279:Carcinoma 256, Walker / Q000201:enzymology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003515:Cycloleucine / Q000494:pharmacology; D004790:Enzyme Induction; D006710:Homocysteine / Q000378:metabolism; D007700:Kinetics; D008223:Lymphoma / Q000201:enzymology; D008715:Methionine / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology
D011073:Polyamines; D006710:Homocysteine; D003515:Cycloleucine; C002373:monobutyryl cyclic AMP; D003994:Bucladesine; D008715:Methionine; D000242:Cyclic AMP; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase