Methionine regulation of N-5-methyltetrahydrofolate: homocysteine methyltransferase and its influence on the growth and protein synthesis in normal, neoplastic, and transformed cells in culture.
Normal human embryonic fibroblasts (CLV-58) and normal embryonic rat fibroblasts (REF) revealed equal growth in media containing 0.2 mM DL-homocysteine thiolactone (HOM) or in methionine (METH) enriched with 1.5 microM cyanocobalamin and 0.1 mM folic acid, whereas L 5178Y lymphoblasts and transformed rat fibroblasts (REF-S) showed more or less acute need for exogenous METH. In normal cells general protein synthesis remained unimpaired during 24 hours after substitution of METH by HOM. In L 5178Y and REF-S cells, however, protein synthesis was significantly inhibited. Measurements of N-5-methyltetrahydrofolate:homocysteine methyltransferase revealed a two- to threefold increase of enzyme activity in normal cells grown on HOM and in L 5178Y and REF-S cells grown on HOM with added METH. HeLa cells showed variability in growth pattern, in general protein synthesis response, and in inducibility of methyltransferase upon substitution of METH by HOM.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004790:Enzyme Induction; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D050904:Homocysteine S-Methyltransferase; D006801:Humans; D008715:Methionine / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism*; D011247:Pregnancy; D014176:Protein Biosynthesis; D051381:Rats
D006710:Homocysteine; D008715:Methionine; D008780:Methyltransferases; D050904:Homocysteine S-Methyltransferase