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. 1975 Sep;72(9):3551–3555. doi: 10.1073/pnas.72.9.3551

Central role for magnesium in coordinate control of metabolism and growth in animal cells.

H Rubin
PMCID: PMC433033  PMID: 171666

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atkinson D. E. The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry. 1968 Nov;7(11):4030–4034. doi: 10.1021/bi00851a033. [DOI] [PubMed] [Google Scholar]
  2. Balk S. D., Whitfield J. F., Youdale T., Braun A. C. Roles of calcium, serum, plasma, and folic acid in the control of proliferation of normal and Rous sarcoma virus-infected chicken fibroblasts. Proc Natl Acad Sci U S A. 1973 Mar;70(3):675–679. doi: 10.1073/pnas.70.3.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bissell M. J., Hatié C., Rubin H. Patterns of glucose metabolism in normal and virus-transformed chick cells in tissue culture. J Natl Cancer Inst. 1972 Aug;49(2):555–565. [PubMed] [Google Scholar]
  4. Blasie J. K., Worthington C. R. Molecular localization of frog retinal receptor photopigment by electron microscopy and low-angle X-ray diffraction. J Mol Biol. 1969 Feb 14;39(3):407–416. doi: 10.1016/0022-2836(69)90135-1. [DOI] [PubMed] [Google Scholar]
  5. Dulbecco R., Elkington J. Induction of growth in resting fibroblastic cell cultures by Ca++. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1584–1588. doi: 10.1073/pnas.72.4.1584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fodge D. W., Rubin H. Activation of phosphofructokinase by stimulants of cell multiplication. Nat New Biol. 1973 Dec 12;246(154):181–183. doi: 10.1038/newbio246181a0. [DOI] [PubMed] [Google Scholar]
  7. Moscatelli D., Rubin H. Increased hyaluronic acid production on stimulation of DNA synthesis in chick embryo fibroblasts. Nature. 1975 Mar 6;254(5495):65–66. doi: 10.1038/254065a0. [DOI] [PubMed] [Google Scholar]
  8. Rein A., Rubin H. Effects of local cell concentrations upon the growth of chick embryo cells in tissue culture. Exp Cell Res. 1968 Mar;49(3):666–678. doi: 10.1016/0014-4827(68)90213-9. [DOI] [PubMed] [Google Scholar]
  9. Rose I. A. The state of magnesium in cells as estimated from the adenylate kinase equilibrium. Proc Natl Acad Sci U S A. 1968 Nov;61(3):1079–1086. doi: 10.1073/pnas.61.3.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rubin H. Inhibition of DNA synthesis in animal cells by ethylene diamine tetraacetate, and its reversal by zinc. Proc Natl Acad Sci U S A. 1972 Mar;69(3):712–716. doi: 10.1073/pnas.69.3.712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rubin H., Koide T. Inhibition of DNA synthesis in chick embryo cultures by deprivation of either serum or zinc. J Cell Biol. 1973 Mar;56(3):777–786. doi: 10.1083/jcb.56.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sanui H. pH dependence of the effect of adenosine triphosphate and ethylenediaminetetraacetate on sodium and magnesium binding by cellular membrane fragments. J Cell Physiol. 1970 Jun;75(3):361–368. doi: 10.1002/jcp.1040750312. [DOI] [PubMed] [Google Scholar]
  13. Sefton B. M., Rubin H. Stimulation of glucose transport in cultures of density-inhibited chick embryo cells. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3154–3157. doi: 10.1073/pnas.68.12.3154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Singh V. N., Singh M., August J. T., Horecker B. L. Alterations in glucose metabolism in chick-embryo cells transformed by Rous sarcoma virus: intracellular levels of glycolytic intermediates. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4129–4132. doi: 10.1073/pnas.71.10.4129. [DOI] [PMC free article] [PubMed] [Google Scholar]

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