Electron and Proton Flow in Hepatocytes During Fatty Acid and Pyruvate Oxidation: Implications for Energy Transduction and Heat Production

  • M. N. Berry
  • R. B. Gregory
  • A. R. Grivell
  • J. W. Phillips
  • P. G. Wallace
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 127)


Since the discovery of the process of oxidative phosphorylation, biochemical textbooks have tacitly assumed that most, if not all, of mammalian mitochondrial respiration is tightly coupled to ATP turnover, so that any increase in cellular oxygen uptake (JO) must necessarily indicate an augmented demand for ATP. On the other hand, much evidence has now accrued that the increase in JO observed when hepatocytes are presented with substrates, particularly fatty acids (Berry, 1974a; Williamson et al., 1969; Debeer et al., 1974; Berry et al., 1983a), cannot be wholly or even mainly accounted for by increased utilization of ATP in biosynthetic processes such as gluconeogenesis and urea formation (Berry, 1974a; Berry et al., 1983a; Hems et al., 1966; Krebs et al., 1964). The mechanism by which oxygen consumption is stimulated to a greater extent than predicted from any increased metabolic activity of the cells has not been established unequivocally. Possibilities include uncoupling of the mitochondria (Scholz et al., 1984; Soboll and Stucki, 1985), changes in eficiency of coupling, perhaps by alterations in the H+/e- ratio of mitochondrial proton pumping (Nicholls, 1974; Pietrobon et al., 1981), induction of futile cycles of ATP synthesis and hydrolysis (Debeer et al., 1974; Newsholme and Crabtree, 1976; Katz and Rognstad, 1976; Plomp et al., 1985), or stimulation of some other pathway such as reversed electron flow (Berry et al., 1983a). None of these explanations seems entirely satisfactory.


Mitochondrial Membrane Mitochondrial Membrane Potential Krebs Cycle Energy Transduction Adenine Nucleotide Translocase 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Azzi, A., 1969 Biocohem. Biophyst Res Cmmun, 37:254.CrossRefGoogle Scholar
  2. Beeckmans, S. and Kanarek, L., 1981, Eur. J, Biochem., 117:527.CrossRefGoogle Scholar
  3. Berry, M.N., 1974a, in: “Regulation of Hepatic Metabolism”, Lundquist, F. and Tygstrup, N., eds., Munksgaard, Copenhagen.Google Scholar
  4. Berry, M.N., 1974b, Methods Enzymol, 32:625.PubMedCrossRefGoogle Scholar
  5. Berry, M.N. and Friend, D.S., 1966 J. Cell Biol. 43:506.CrossRefGoogle Scholar
  6. Berry, M.N., Clark, D.G., Grivell, A.R. and Wallace, P.G., 1983a., Eur. J. Biochem., 131:205.PubMedCrossRefGoogle Scholar
  7. Berry, M.N., Gregory, R.B., Grivell, A.R., and Wallace, P.G., 1983b, Eur. J. Biochem., 131:215.PubMedCrossRefGoogle Scholar
  8. Boyer, P.D., 1975, FEBS Lett. 58:1.PubMedCrossRefGoogle Scholar
  9. Boyer, P.D., 1977, Trends Biochem. Sci. 2:38.CrossRefGoogle Scholar
  10. Brand, M.D. and Felber, S.M., 1984, Biochem. J. 217:453.PubMedGoogle Scholar
  11. Campo, M.L., Zhang, C.-J. and Tedeschi, H., 1984, Biochem. Soc. Trans., 12:384.PubMedGoogle Scholar
  12. Clark, A.J., Cotton, N.P.J. and Jackson, J.B., 1983, Biochim. Biophvs. Acta, 723:440.CrossRefGoogle Scholar
  13. Cohen, S.M., Ogawa, S., Rottenberg, H., Glynn, P., Yamane, T., Brown, T.R., and Shulman, R.G., 1978, Nature. 273:554.PubMedCrossRefGoogle Scholar
  14. Debeer, L.J., Mannaerts, G. and DeSchepper, P., 1974, Eur. J. Biochem., 47:591.PubMedCrossRefGoogle Scholar
  15. Degenaar, C.P., 1983, Clin. Chim. Acta., 131:155.PubMedCrossRefGoogle Scholar
  16. Ferguson, S.J. and Sorgato, M.C., 1982, Ann. Rev. Biochem., 51:185.PubMedCrossRefGoogle Scholar
  17. Filiingame, R.H., 1980, Ann. Rev. Biochem., 49:1079.CrossRefGoogle Scholar
  18. Hems, R., Ross, B.D., Berry, M.N. and Krebs, H.A., 1966, Biochem. J., 101:284.PubMedGoogle Scholar
  19. Higuti, T., 1984, Molep, Cellt Biochem., 61:37.Google Scholar
  20. Hoek, J.B., Nicholls, D.G. and Williamson, J.R., 1980, J. Biol. Chem., 255:1458.PubMedGoogle Scholar
  21. Katz, J. and Rognstad, R., 1976, Curr. Top. Cell Reg., 10:237.Google Scholar
  22. Kell, D.B. and Morris, J.G., 1981, la: “Vectorial Reactions in Electron and Ion Transport in Mitochondria and Bacteria”, F. Palmieri, F. Quagliariello, N. Siliprandi and E. C. Slater, eds., Elsevier/Norths Holland, Amsterdam.Google Scholar
  23. Kiorpes, T.C., Hoerr, D., Ho, W., Weaner, L.E., Inman, M.G. and Tutwiler, G.F., 1984, J. Biol. Chem., 259:9750.PubMedGoogle Scholar
  24. Knox, B.E. and Tsong, T.Y., 1984, J. Biol. Chem., 259:4757.PubMedGoogle Scholar
  25. Krebs, H.A., Dierks, C. and Gascoyne, T., 1964, Biochem. J., 93:112.PubMedGoogle Scholar
  26. Krebs, H.A., Cornell, N.W., Lund, P. and Hems, R., 1974, In: “Regulation of Hepatic Metabolism”, F. Lundquist and N. Tygstrup, eds., Munksgaard, Copenhagen.Google Scholar
  27. Malpress, F.M., 1984, Biochem. Soc. Trans., 12:399.PubMedGoogle Scholar
  28. Matlib, M.A. and O’Brien, P.J., 1975, Arch Biochem Biophry., 167:193.CrossRefGoogle Scholar
  29. McClare, C.W.F., 1971, J. Theor. Biol., 30:1.PubMedCrossRefGoogle Scholar
  30. Mitchell, P., 1961, Nature. 191:144.PubMedCrossRefGoogle Scholar
  31. Mitchell, P., 1976, Biochem. Soc. Trans., 4:399.PubMedGoogle Scholar
  32. Mitchell, P., Mitchell, R., Moody, A.J., West, I.C., Baum, H. and Wrigglesworth, J.M., 1985, FEBS Lett., 188:1.PubMedCrossRefGoogle Scholar
  33. Newsholme, E.A. and Crabtree, B., 1976, Biochem. Soc. Symp., 41:61.PubMedGoogle Scholar
  34. Nicholls, D.G., 1974, Eur. J. Biochem.. 50:305.PubMedCrossRefGoogle Scholar
  35. Nordenbrand, K. and Ernster, L., 1971, Eur. J. Biochem., 18:258.PubMedCrossRefGoogle Scholar
  36. O’Shea, P.S. and Chappell, J.B., 1984, Biochem. J., 219:401.PubMedGoogle Scholar
  37. Pietrobon, D., Azzone, G.F. and Walz, D., 1981, Eur. J. Biochem., 117:389.PubMedCrossRefGoogle Scholar
  38. Pietrobon, D., Zoratti, M. and Azzone, G.F., 1983 Biochim. Biophvs. Acta., 723:317.CrossRefGoogle Scholar
  39. Plomp, P.J.A.M., van Roermund, C.W.T., Groen, A.K., Meijer, A.J., and Tager, J.M., 1985, FEBS Lett. 193:243.PubMedCrossRefGoogle Scholar
  40. Rosing, J., Kay alar, C. and Boyer, P.D., 1977, J. Biol. Chem., 252:2478.PubMedGoogle Scholar
  41. Sohlodder, E., Graber, P. and Witt, H.T., 1982, in: “Electron Transport and Photophosphorylation”, J. Barber, ed., Elsevier, Amsterdam.Google Scholar
  42. Scholz, R., Schwabe, U. and Soboll, S., 1984, Eur. J. Bioohem. 141:223.CrossRefGoogle Scholar
  43. Seren, S., Caporin, G., Galiazzo, F., Lippe, G., Ferguson, S.J. and Sorgato, M.C., 1985, Eur. J. Biochem., 152:373.PubMedCrossRefGoogle Scholar
  44. Soboll, S. and Stucki J., 1985, Biochem., Biophyst Acta, 807:245.CrossRefGoogle Scholar
  45. Srere, P.A., Halper, L.A. and Finkelstein, M.B., 1978, in: “Microenvironments and Metabolic Compartmentation”, P.A. Srere and R. W. Estabrook, eds., Academic Press, New York.Google Scholar
  46. Sumegi, B. and Srere, P.A., 1984, J. Biol. Chem., 259:8748.PubMedGoogle Scholar
  47. Sumegi, B., Gilbert, H.F. and Srere, P.A., 1985, J. Biol. Chem., 260:188PubMedGoogle Scholar
  48. Teissie, J., Knox, B.E., Tsong, T.Y. and Wehrle, J., 1981 Proo. Natl. Aeadt Sci U.S.A. 78:7473.CrossRefGoogle Scholar
  49. Welch, G.R. and Kell, D.B., 1986, in: “The Fluctuating Enzyme”, G.R. Welch, ed., Wiley-Interscience, New York.Google Scholar
  50. Westerhoff, H.V., Melandri, B.A., Venturoli, G., Azzone, G.F. and Kell, D.B., 1984 FEBS Lett. 165:1.PubMedCrossRefGoogle Scholar
  51. Williams, R.J.P., 1978, Biochem., Biophys Acta 505:1.Google Scholar
  52. Williamson, J.R., Scholz, R., Browning, E.T., Thurman, R.G. and Fukami, M.H., 1969, J. Biol. Chem. 244:5044.PubMedGoogle Scholar
  53. Witt, H., Schlodder, E. and Graber, P., 1976, FEBS Lett. 69:272.PubMedCrossRefGoogle Scholar
  54. Woods, H.F., Eggleston, L.V. and Krebs, H.A., 1970 Biochem. J., 119:501PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • M. N. Berry
    • 1
  • R. B. Gregory
    • 1
  • A. R. Grivell
    • 1
  • J. W. Phillips
    • 1
  • P. G. Wallace
    • 1
  1. 1.Department of Biochemistry School of MedicineFlinders University of South AustraliaBedford ParkAustralia

Personalised recommendations