Metabolic Brain Disease

, Volume 5, Issue 3, pp 111–118 | Cite as

Resistance of brain phosphofructo-1-kinase to pH-dependent inhibition

  • Sergio E. Bazaes
  • Robert G. Kemp
Original Contributions

Abstract

The kinetic regulatory properties of rabbit brain phosphofructo-1-kinase (PFK), which consists of a mixture of heterotetramers containing A, B, and C isozymic subunits, were found to be much less responsive to pH than the properties of skeletal muscle PFK, the A4 isozyme. The muscle enzyme was strongly inhibited at low pH as a result of a striking increase in the allosteric interaction coefficient or Hill coefficient at pH values below 7.3. This phenomenon was not seen with the brain enzyme. This property of brain PFK may protect this organ, which is exclusively dependent on glucose metabolism, by permitting continued glycolysis despite decreases in intracellular pH.

Key words

brain phosphofructokinase isozymes allosteric properties pH glycolysis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal. Biochem. 72: 248–254.Google Scholar
  2. Cottreau, D., Levin, M. J., Kahn, A. (1979). Purification and partial characterization of different forms of phosphofructokinase in man.Biochim. Biophys. Acta 568: 183–194.Google Scholar
  3. Dombrowski, G. J., Jr., Swiatek, K. R., and Chao, K.-L. (1989). Lactate, 3-hydroxybutyrate, and glucose as substrates for the early postnatal rat brain.Neurochem. Res. 14: 667–675.Google Scholar
  4. Dunaway, G. A., and Kasten, T. P. (1985). Nature of the rat brain 6-phosphofructo-1-kinase isozymes.J. Biol. Chem. 260: 4180–4185.Google Scholar
  5. Dunaway, G. A., and Kasten, T. P. (1987). Nature of the subunits of the 6-phosphofructo-1-kinase isoenzyme from rat tissues.Biochem. J. 242: 667–671.Google Scholar
  6. Dunaway, G. A., and Kasten, T. P. (1988). Physiological implications of the alteration of 6-phosphofructo-1-kinase isozyme pools during brain development and aging.Brain Res. 456: 310–316.Google Scholar
  7. Foe, L. G., and Kemp, R. G. (1984). Isozyme composition and phosphorylation of brain phosphofructokinase.Arch. Biochem. Biophys. 228: 503–511.Google Scholar
  8. Gonzalez, F., and Kemp, R. G. (1978). The A2B2 hybrid isozyme of phosphofructokinase.J. Biol. Chem. 253: 1493–1497.Google Scholar
  9. Kemp, R. G. (1975). Phosphofructokinase from rabbit skeletal muscle.Methods Enzymol 42C: 71–72.Google Scholar
  10. Kemp, R. G., and Foe, L. G. (1983). Allosteric regulatory properties of muscle phosphofructokinase.Mol. Cell. Biochem. 57: 147–154.Google Scholar
  11. Lowry, O. H., and Passonneau, J. V. (1964). The relationship between substrates and enzymes of glycolysis in brain.J. Biol. Chem. 239: 31–42.Google Scholar
  12. Lowry, O. H., and Passonneau, J. V. (1966). Kinetic evidence for multiple binding sites on phosphofructokinase.J. Biol. Chem. 241: 2268–2279.Google Scholar
  13. Paschen, W., Djuricic, B., Mies, G., Schmidt-Kastner, and Linn, F. (1987). Lactate and pH in the brain: Association and dissociation in different pathophysiological states.J. Neurochem. 48: 154–159.Google Scholar
  14. Paetkau, V., and Lardy, H. A. (1967). Phosphofructokinase. Correlation of physical and enzymatic properties.J. Biol. Chem. 242: 2035–2042.Google Scholar
  15. Smith, M.-L., von Hanwehr, R., and Siesjo, B. K. (1986). Changes in extra- and intracellular pH in the brain during and following ischemia in hyperglycemic and in moderately hypoglycemic rats.J. Cereb. Blood Flow Metab. 6: 574–583.Google Scholar
  16. Trivedi. B., and Danforth, W. H. (1966). Effect of pH on the kinetics of frog muscle phosphofructokinase.J. Biol. Chem. 241: 4110–4114.Google Scholar
  17. Tsai, M. Y., and Kemp, R. G. (1974). Rabbit brain phosphofructokinase.J. Biol. Chem. 249: 6590–6596.Google Scholar
  18. Uyeda, K. (1979). Phosphofructokinase.Adv. Enzymol Relat. Areas Mol. Biol. 48: 193–244.Google Scholar

Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Sergio E. Bazaes
    • 1
  • Robert G. Kemp
    • 1
  1. 1.Department of Biological Chemistry and StructureUniversity of Health Sciences/The Chicago Medical SchoolNorth Chicago

Personalised recommendations