Calcium Ions, Hormones, and Mammalian Oxidative Metabolism

  • James G. McCormack
  • Richard M. Denton
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Many hormones and other external stimuli are known to act on mammalian cells by causing increases in the cytoplasmic concentration of Ca2+ . In most if not all cases, the effects brought about, e.g., contraction, secretion, and so on, require an increased supply of ATP. One possible mechanism whereby this increased energy demand may be met in some tissues is by a concommitant enhancement by Ca2+ of glycogen breakdown and hence glycolysis through the activation of phosphorylase kinase. In this paper we review the evidence for another potential mechanism whereby increases in Ca2+ may affect rates of metabolism and hence ATP synthesis, and which may be of more general importance. This mechanism involves the relay of the increases in cytoplasmic Ca2+ into the mitochondrial matrix resulting in the activation of three oxidative dehydrogenases which play key roles in the supply of NADH to the respiratory chain for ATP production.


Pyruvate Dehydrogenase Liver Mitochondrion Phosphorylase Kinase Glycogen Breakdown Mammalian Mitochondrion 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Assimacopoulos-Jeannet, F. D., McCormack, J. G., and Jeanrenaud, B., 1986, Vasopressin and/or glucagon rapidly increases mitochondrial calcium and oxidative enzyme activities in the perfused rat liver, J. Biol. Chem. 261:8799–8804.PubMedGoogle Scholar
  2. Crompton, M., Kessar, P., and Al-Nasser, I., 1983, The a-adrenergic mediated activation of the mitochondrial Ca2+ uniporter and its role in the control of intramitochondrial Ca2+ in vivo, Biochem. J. 216:333–342.PubMedGoogle Scholar
  3. Denton, R. M., and McCormack, J. G., 1980, On the role of the calcium transport cycle in heart and other mammalian mitochondria, FEBS Lett. 119:1–8.PubMedCrossRefGoogle Scholar
  4. Denton, R. M., and McCormack, J. G., 1985, Ca2+ -transport by mammalian mitochondria and its role in hormone action, Am. J. Physiol. 249:E543–E554.PubMedGoogle Scholar
  5. Denton, R. M., McCormack, J. G., and Edgell, N. J., 1980, Role of calcium ions in the regulation of intramitochondrial metabolism: Effects of Na+, Mg2+ and ruthenium red on the Ca2+ -stimulated oxidation of oxoglutarate and on pyruvate dehydrogenase activity in intact rat heart mitochondria, Biochem. J. 190:107–117.PubMedGoogle Scholar
  6. Goldstone, T. P., Duddridge, R. J., and Crompton, M., 1983, The activation of the Na + -dependent efflux pathway of Ca2+ from liver mitochondria by glucagon and ß-adrenergic agonists, Biochem. J. 210:463–472.PubMedGoogle Scholar
  7. Hansford, R. G., 1985, Relation between mitochondrial calcium transport and control of energy metabolism, Rev. Physiol. Biochem. Pharmacol. 102:1–72.PubMedCrossRefGoogle Scholar
  8. Hansford, R. G., 1987, Relation between cytosolic free Ca2+ concentration and the control of pyruvate dehydrogenase in isolated cardiac myocytes, Biochem. J. 241:145–151.PubMedGoogle Scholar
  9. Hayat, L. H., and Crompton, M., 1982, Evidence for the existence of regulatory sites for Ca2+ on the Na+/Ca2+ carrier of cardiac mitochondria, Biochem. J. 176:627–629.Google Scholar
  10. Marshall, S. E., McCormack, J. G., and Denton, R. M., 1984, Role of Ca2+ ions in the regulation of intramitochondrial metabolism in rat epididymal adipose tissue: Evidence against a role for Ca2+ in the activation of pyruvate dehydrogenase by insulin, Biochem. J. 218:249–260.PubMedGoogle Scholar
  11. McCormack, J. G., 1985a, Characterisation of the effects of Ca2+ on the intramitochondrial Ca2+ -sensitive enzymes from rat liver and within rat liver mitochondria, Biochem. J. 231:581–595.PubMedGoogle Scholar
  12. McCormack, J. G., 1985b, Studies on the activation of rat liver pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase by adrenaline and glucagon: Role of increases in intramitochondrial Ca2+ concentration, Biochem. J. 231:597–608.PubMedGoogle Scholar
  13. McCormack, J. G., and Denton, R. M., 1984, Role of Ca2+ in the regulation of intramitochondrial metabolism in rat heart: Evidence from studies with isolated mitochondria that adrenaline activates the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes by increasing the intramitochondrial concentration of Ca2+, Biochem. J. 218:235–247.PubMedGoogle Scholar
  14. McCormack, J. G., and Denton, R. M., 1986, Ca2+ as a second messenger within mitochondria, Trends Biochem. Sci. 11:258–262.CrossRefGoogle Scholar
  15. McCormack, J. G., and England, P. J., 1983, Ruthenium red inhibits the activation of pyruvate dehydrogenase caused by positive inotropic agents in the perfused rat heart, Biochem. J. 214: 581–585.PubMedGoogle Scholar
  16. Midgley, P. J. W., Rutter, G. A., Thomas, A. P. and Denton, R. M., 1987, Effects of Ca2+ and Mg2+ on the activity of pyruvate dehydrogenase phosphate phosphatase within toluene-permeabilized mitochondria, Biochem. J. 241:371–377.PubMedGoogle Scholar
  17. Nicholls, D. G., and Akerman, K. E. O., 1982, Mitochondrial calcium transport, Biochim. Biophys. Acta 683:57–88.PubMedGoogle Scholar
  18. Somlyo, A. P., Bond, M., and Somlyo, A. V., 1985, Calcium content of mitochondria and endoplasmic reticulum in liver frozen rapidly in vivo, Nature 314:622–625.PubMedCrossRefGoogle Scholar
  19. Taylor, W. M., Prpic, V., Exton, J. H., and Bygrave, F. L., 1980, Stable changes to calcium fluxes in mitochondria isolated from rat livers perfused with adrenergic agonists and with glucagon, Biochem. J. 188:443–450.PubMedGoogle Scholar
  20. Vághy, P. L., Johnson, T. D., Matlib, M. A., Wang, T., and Schwarz, A., 1982, Selective inhibition of Na+-induced Ca2+ release from heart mitochondria by diltiazem and certain other Ca2+ antagonist drugs, J. Biol. Chem. 257:6000–6002.PubMedGoogle Scholar
  21. Wendt-Gallitelli, M. F., 1986, Ca-pools involved in the regulation of cardiac contraction under positive inotropy. X-ray microanalysis on rapidly-frozen ventricular muscles of guinea-pig, Basic Res. Cardiol. 81:25–32.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • James G. McCormack
    • 1
  • Richard M. Denton
    • 2
  1. 1.Department of BiochemistryUniversity of LeedsLeedsUK
  2. 2.Department of BiochemistryUniversity of Bristol Medical SchoolBristolUK

Personalised recommendations