title: Central role for magnesium in coordinate control of metabolism and growth in animal cells.
abstract: The rate of DNA synthesis in cultures of chicken embryo fibroblasts is reduced by deprivation of serum, high population density, and other "physiological" effectors, through a reduction in the number of cells in the S-period of the cell cycle. The same effect can be produced by drastically reducing the concentration of Mg++ added to the medium. This effect is erratic, however, and better control of [Mg++] can be achieved with phosphorylated compounds which preferentially bind Mg++. Both ATP and ADP, at concentrations in the medium less than or equal to [Mg++], stimulate DNA synthesis in cultures, and at greater concentrations inhibit DNA synthesis by affe-ting the proportion of cells in the S-period. Sodium pyrophosphate, which strongly complexes Mg++, causes little stimulation of DNA synthesis at low concentrations, but causes a striking decrease at concentrations exceeding [Mg++] of the medium. The inhibition can be fully reversed by adding an excess of Mg++, and the kinetics of increase in DNA synthesis resemble those which follow the restoration of serum to serum-deprived cultures. Limitation of [Mg++] by pyrophosphate also reduces the rates of RNA and protein synthesis, 2-deoxy-D-glucose uptake, and lactic acid production to an extent comparable to the reduction caused by the removal of serum from the medium. A model for the coordinate control of metabolism, differentiated function, and growth through the activity of divalent cations is described. The compartmentalization of Mg++ within the cell serves as the key element in this coordinate control by regulating those metabolic pathways in which the rate-limiting steps are transphosphorylation reactions.
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D003847:Deoxyglucose / Q000378:metabolism; D003864:Depression, Chemical; D011756:Diphosphates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007773:Lactates / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000227:Adenine Nucleotides; D011756:Diphosphates; D007773:Lactates; D004247:DNA; D003847:Deoxyglucose; D008274:Magnesium; D002118:Calcium