Advertisement

Application of Physical Methods to the Study of Enzymes Containing Bound Manganese: Problems and Prospects

  • Michael C. Scrutton
  • G. H. Reed
  • A. S. Mildvan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 40)

Abstract

Although manganese has been long recognized as an essential micronutrient for a variety of organisms (I), the physiological basis for this metal requirement remained obscure for many years. Thus, despite the demonstration that numerous enzymes which exhibit a requirement for activation by Me2+, e.g., kinases, synthetases, some dehydrogenases, can utilize Mn2+ at lower concentrations than Mg2, the relative concentrations of these two metal ions present in most tissues and species (2) indicate that Mg2+ is likely to serve as the activating metal ion under in vivo conditions. The recent discovery of bound manganese as a component of several proteins has provided a rationale for the unique biological role of this metal ion. Nuclear magnetic resonance (NMR) studies were responsible for providing the first indication of the existence of protein-bound manganese. In these studies pyruvate carboxylase from chicken liver was found to cause a marked increase in the longitudinal nuclear magnetic relaxation rate (1/T1) of water protons indicating the presence of a bound paramagnetic component in this enzyme.

Keywords

Pyruvate Carboxylase Water Proton Partial Reaction Macromolecular Complex Coordination Scheme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cotzias, G. C. (1958), Physiol. Revs., 38, 503.Google Scholar
  2. 2.
    Thiers, R. E. and Vallée, B. L. (1957), J. Biol. Chem., 226, 911.PubMedGoogle Scholar
  3. 3.
    Scrutton, M. C., Utter, M. F., and Mildvan, A. S. (1966), J. Biol. Chem., 241, 3480.PubMedGoogle Scholar
  4. 4.
    Scrutton, M. C. and Mildvan. A. S. (1968), Biochemistry, 7, 1490.PubMedCrossRefGoogle Scholar
  5. 5.
    Scrutton, M. C., Griminger, P., and Wallace, J. C. (1972), J. Biol. Chem., 247, 3305.PubMedGoogle Scholar
  6. 6.
    Scrutton, M. C., Young, M. R., and Utter, M. F. (1970), J. Biol. Chem., 245, 6620.Google Scholar
  7. 7.
    Agrawal, B. B. L. and Goldstein, I. J. (1968), Arch. Biochem. Biophys., 124, 218.PubMedCrossRefGoogle Scholar
  8. 8.
    Dieckert, J. W. and Rozacky, E. (1969), Arch. Biochem. Biophys., 134, 373.CrossRefGoogle Scholar
  9. 9.
    Keele, B. B., McCord, J. M., and Fridovich, I. (1970), J. Biol. Chem., 245, 6176.PubMedGoogle Scholar
  10. 10.
    Vance, P. G., Keele, B. B., and Rajagopalan, K. V. (1972), J. Biol. Chem., 247, 4782.PubMedGoogle Scholar
  11. 11.
    Scrutton, M. C. (1971), Biochemistry, 10, 3897.PubMedCrossRefGoogle Scholar
  12. 12.
    Carrico, R. J. and Deutsch, H. F. (1970), J. Biol. Chem., 245, 723.PubMedGoogle Scholar
  13. 13.
    McCord, J. M. and Fridovich, I. (1969), J. Biol. Chem., 244, 6049.PubMedGoogle Scholar
  14. 14.
    Wilgus, H. S., Norris, L. C., and Heuser, G. L. (1936), Science, 84, 252.PubMedCrossRefGoogle Scholar
  15. 15.
    Mildvan, A. S. and Cohn, M. (1970), Adv. in Enzymol., 33, I.Google Scholar
  16. 16.
    Swift, T. J. and Connick, R. E. (1962), J. Chem. Phys., 37, 307.CrossRefGoogle Scholar
  17. 17.
    Luz, Z. and Meiboom, S. (1964), J. Chem. Phys., 40, 2686.CrossRefGoogle Scholar
  18. 18.
    Solomon, I. (1955), Phys. Rev., 99, 559.CrossRefGoogle Scholar
  19. 19.
    Bloembergen, N. (1957), J. Chem. Phys., 27, 572.CrossRefGoogle Scholar
  20. 20.
    Eisinger, J., Shulman, R. G., and Szymanski, B. M. (1962), J. Chem. Phys., 36, 1721.CrossRefGoogle Scholar
  21. 21.
    Luz, Z. and Shulman, R. G. (1965), J. Chem. Phys., 43, 3750.CrossRefGoogle Scholar
  22. 22.
    Mildvan, A. S. and Cohn, M. (1966), J. Biol. Chem., 241, 1178.PubMedGoogle Scholar
  23. 23.
    Cohn, M. and Leigh, J. S. (1962), Nature, 193, 1037.PubMedCrossRefGoogle Scholar
  24. 24.
    Eisinger, J., Shulman, R. G., and Blumberg, W. E. (1961), Nature, 192, 963.PubMedCrossRefGoogle Scholar
  25. 25.
    Letter, M. S., Grant, M. W., Wood, E. J., Dodgen, H. W., and Hunt, J. P. (1972), Inorg. Chem., 11, 2701.CrossRefGoogle Scholar
  26. 26.
    Reuben, J. and Cohn, M. (1970), J. Biol. Chem., 245, 6539.PubMedGoogle Scholar
  27. 27.
    Reed, G. H., Diefenbach, H., and Cohn, M. (1972), J. Biol. Chem., 247, 3066.PubMedGoogle Scholar
  28. 28.
    Peacocke, A. R., Richards, R. E., and Sheard, B. (1969), Mol. Physics, 16, 177.Google Scholar
  29. 29.
    Montgomery, H., Chastain, R. V., and Lingalfelter, E. C. (1966), Acta Crystallogr., 20, 731.CrossRefGoogle Scholar
  30. 30.
    Leigh, J. S. (1971), Ph.D. Thesis, Univ. of Pennsylvania.Google Scholar
  31. 31.
    Mildvan, A. S. and Scrutton, M. C. (1967), Biochemistry, 6, 2978.PubMedCrossRefGoogle Scholar
  32. 32.
    Nowak, T. and Mildvan, A. S. (1972), Biochemistry, 11, 2819.PubMedCrossRefGoogle Scholar
  33. 33.
    Jones, R., Dwek, R. A., and Walker, I. O. (1972), Europ. J. Biochem., 28, 74.PubMedCrossRefGoogle Scholar
  34. 34.
    Barfield, M. and Karplus, M. (1969), J. Am. Chem. Soc, 91, I.Google Scholar
  35. 35.
    Scrutton, M. C., Keech, D. B., and Utter, M. F. (1965), J. Biol. Chem., 240, 574.PubMedGoogle Scholar
  36. 36.
    Mildvan, A. S., Scrutton, M. C., and Utter, M. F. (1966), J. Biol. Chem., 241, 3488.PubMedGoogle Scholar
  37. 37.
    King, J. and Davidson, N. (1958), J. Chem. Phys., 29, 787.CrossRefGoogle Scholar
  38. 38.
    Hoard, J. L., Pedersen, B., Richards, S., and Silverton, J. V. (1961), J. Am. Chem. Soc, 83, 3533.CrossRefGoogle Scholar
  39. 39.
    Scrutton, M. C. and Mildvan, A. S. (1970), Arch. Biochem. Biophys., 140, 131.PubMedCrossRefGoogle Scholar
  40. 40.
    Reed, G. H. and Scrutton, M. C. Unpublished data.Google Scholar
  41. 41.
    Fung, C. H., Mildvan, A. S., Allerhand, A., Komoroski, R., and Scrutton, M. C. (1973), Biochemistry, 13, in press.Google Scholar
  42. 41A.
    A. Reed, G. H., Leigh, J. S., and Pearson, J. E. (1971), J. Chem. Phys., 55, 3311.CrossRefGoogle Scholar
  43. 42.
    Cohn, M. and Reuben, J. (1971), Accounts. Chem. Res., 4, 214.CrossRefGoogle Scholar
  44. 43.
    Irias, J. J., Olmsted, M. R., and Utter, M. F. (1969), Biochemistry, 8, 5136.PubMedCrossRefGoogle Scholar
  45. 44.
    Reed, G. H. and Ray, W. J. (1971), Biochemistry, 10, 3190.PubMedCrossRefGoogle Scholar
  46. 45.
    Reed, G. H. and Cohn, M. (1972), J. Biol. Chem., 247, 3073.PubMedGoogle Scholar
  47. 45A.
    Wolfenden, R. (1972), Accounts. Chem. Res., 5, 10.CrossRefGoogle Scholar
  48. 46.
    Reed, G. H. Unpublished data.Google Scholar
  49. 47.
    Novoa, W. B., Winer, A. D., Glaid, A. J., and Schwert, G. W. (1959), J. Biol. Chem., 234, 1143.PubMedGoogle Scholar
  50. 48.
    Terayama, M. and Vestling, C. (1956), Biochem. Biophys. Acta, 20, 586.PubMedCrossRefGoogle Scholar
  51. 49.
    Pfleiderer, G., Jackel, D., and Wieland, T. (1958), Biochem. Z., 330, 296.PubMedGoogle Scholar
  52. 50.
    Rose, I. A. (1970), J. Biol. Chem., 245, 6025.Google Scholar
  53. 51.
    Scrutton, M. C. and Young, M. R. (1972), vol. 6, p. I, The Enzymes, 3rd ed., P. D. Boyer, ed., New York: Academic Press.Google Scholar
  54. 52.
    Northrop, D. B. and Wood, H. G. (1969), J. Biol. Chem., 244, 5801.PubMedGoogle Scholar
  55. 53.
    Northrop, D. B. (1969), J. Biol. Chem., 244, 5808.PubMedGoogle Scholar
  56. 54.
    Barden, R. E., Fung, C. H., Utter, M. F., and Scrutton, M. C. (1972), J. Biol. Chem., 247, 1723.Google Scholar
  57. 55.
    Scrutton, M. C. and Utter, M. F. (1965), J. Biol. Chem., 240, 3714.PubMedGoogle Scholar
  58. 56.
    Leigh, J. S. (1970), J. Chem. Phys., 52, 2608.CrossRefGoogle Scholar
  59. 57.
    Taylor, J. S., Leigh, J. S., and Cohn, M. (1969), Proc. Natl. Acad. Sci. U. S., 64, 219.CrossRefGoogle Scholar
  60. 58.
    Scrutton, M. C. Unpublished data.Google Scholar
  61. 59.
    Bias, R. and Keech, D. B. (1972), J. Biol. Chem., 247, 3255.Google Scholar
  62. 59a.
    McClure, W. R., Lardy, H. A., and Kneifel, H. P. (1971), J. Biol. Chem., 246, 3569.PubMedGoogle Scholar
  63. 60.
    Cohn, M. and Townsend, J. (1954), Nature, 173, 1090.CrossRefGoogle Scholar
  64. 61.
    Moss, J. and Lane, M. D. (1971), Adv. Enzymol., 35, 321.PubMedGoogle Scholar
  65. 62.
    Schwartz, R. W. and Carlin, R. L. (1970), J. Am. Chem. Soc, 92, 6763.CrossRefGoogle Scholar
  66. 63.
    Cotton, F. A. and Wilkinson, D. (1966), Advanced Inorganic Chemistry, 2nd ed., New York: Interscience.Google Scholar
  67. 64.
    Dingle, R. (1966), Acta Chem. Scand., 20, 33.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1973

Authors and Affiliations

  • Michael C. Scrutton
    • 1
  • G. H. Reed
    • 2
  • A. S. Mildvan
    • 3
  1. 1.Department of BiochemistryTemple University School of MedicinePhiladelphiaUSA
  2. 2.Department of Biophysics and Physical Biochemistry, Johnson Research FoundationUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.The Institute for Cancer ResearchPhiladelphiaUSA

Personalised recommendations