Pflügers Archiv

, Volume 355, Issue 1, pp 27–37 | Cite as

Einfluß von Herzarbeit und Substratangebot auf die Regulation der Pyruvatdehydrogenase-Aktivität an isolierten Meerschweinchenherzen

  • Bernd Schulze Wischeler
  • Ernst R. Müller-Ruchholtz
  • H. Reinauer
Article

Influence of heart work and substrate uptake on the regulation of pyruvate dehydrogenase activity in isolated guinea pig hearts

Summary

In isolated guinea pig hearts performing a defined stroke work, the influence of heart work and substrate uptake on the interconversion of pyruvate dehydrogenase (PDH) was studied.

When hearts from fasted animals are perfused with a salt solution containing 10 mM glucose, an increase in cardiac output and aortic pressure effects an increase in active PDH from 50 to 74% of total PDH activity and a decrease in tissue content of energy-rich phosphates. Pyruvate turnover calculated from oxygen consumption corresponds with PDH activity. Under these experimental conditions, PDH activity might either represent the rate limiting step of oxidative glucose breakdown, or it might be adjusted to a flux rate controlled by other factors. In fed animals, PDH activity exceeds the pyruvate turnover. However, an increase of heart work raises the active PDH from 76 to 95%.

Addition of 10 mM acetate to the perfusion medium decreases PDH activity and glucose uptake. In fed animals, an increase of heart work raises the active PDH from 43 to 59% only, whereas in fasted animals this effect is abolished.

The effect of changes in heart work on PDH interconversion might be explained by changes in energy-rich phosphate concentrations. However, substrate uptake and nutritional state may interfere or even abolish this effect.

Key words

Heart Work Pyruvate Dehydrogenase Energy-Rich Phosphates Substrate Uptake 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Barrera, C. R., Namihira, G., Hamilton, L., Munk, P., Eley, M. H., Linn, T. C., Reed, L. J.: α-Keto acid dehydrogenase complexes. XVI. Studies on the subunit structure of the PDH complexes from bovine kidney and heart. Arch. Biochem. Biophys.148, 343–358 (1972)Google Scholar
  2. 2.
    Bergmeyer, H. U. (Hrsg.): Methoden der enzymatischen Analyse. Weinheim/Bergstraße: Verlag Chemie 1970Google Scholar
  3. 3.
    Bremer, J.: Pyruvate dehydrogenase, substrate specifity and product inhibition. Europ. J. Biochem.8, 535–540 (1969)Google Scholar
  4. 4.
    Garland, P. B., Randle, P. J.: Control of pyruvate dehydrogenase in the perfused rat heart by the intracellular concentration of acetyl-coenzyme A. Biochem. J.91, 6c–7c (1964)Google Scholar
  5. 5.
    Junger, E., Reinauer, H.: Untersuchungen zur Struktur der Pyruvatdehydrogenase aus Schweineherzmuskel. Biochim. biophys. Acta (Amst.)250, 478–490 (1972)Google Scholar
  6. 6.
    Linn, T. C., Pelley, J. W., Pettit, F. H., Hucho, F., Randall, D. D., Reed, L.: α-Keto acid dehydrogenase complexes. XV. Purification and properties of the component enzymes of the pyruvate dehydrogenase complexes from bovine kidney and heart. Arch. Biochem. Biophys.148, 327–342 (1972)Google Scholar
  7. 7.
    Linn, T. C., Pettit, F. H., Hucho, F., Reed, L.: α-Keto acid dehydrogenase complexes. XI. Comparative studies of regulatory properties of the PDH-complexes from kidney, heart, and liver mitochondria. Proc. nat. Acad. Sci. (Wash.)64, 227–234 (1969)Google Scholar
  8. 8.
    Linn, T. C., Pettit, F. H., Reed, L.: α-Keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef-kidney mitochondria by phosphorylation and dephosphorylation. Proc. nat. Acad. Sci. (Wash.)62, 234–241 (1969)Google Scholar
  9. 9.
    Lopes-Cardozo, M., Vaartjes, W. J., Van den Bergh, S. G.: Regulation of pyruvate metabolism by the mitochondrial energy state: the effect of palmityl coenzyme A. FEBS Letters28, 265–269 (1972)Google Scholar
  10. 10.
    Müller-Ruchholtz, E. R., Lochner, W.: Utilization of glycolytic energy for external, heart work. J. molec. Cell. Card.3, 15–29 (1971)Google Scholar
  11. 11.
    Neely, I. R., Denton, R. M., England, P. J., Randle, P. J.: The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart. Biochem. J.128, 147–159 (1972)Google Scholar
  12. 12.
    Newsholme, E. A.: The regulation of phosphofructokinase in muscle. Cardiology56, 22–34 (1971/72)Google Scholar
  13. 13.
    Olson, R. E., Hoeschen, R. J.: Endogenous lipid utilization by the isolated perfused rat heart. Biochem. J.103, 796–801 (1967)Google Scholar
  14. 14.
    Opie, L. H.: Metabolism of the heart in health and disease. Amer. Heart J.76, 685–698 (1968);77, 100–122 (1969)Google Scholar
  15. 15.
    Pande, S. V., Blanchaer, M. C.: Reversible inhibition of mitochondrial adenosine diphosphate phosphorylation by long chain acyl coenzyme A esters. J. biol. Chem.246, 402–411 (1971)Google Scholar
  16. 16.
    Portenhauser, R., Wieland, O.: Regulation of pyruvate dehydrogenase in mitochondria of rat liver. Europ. J. Biochem.31, 308–314 (1972)Google Scholar
  17. 17.
    Reed, L. J., Linn, T. C., Hucho, F., Namihira, G., Barrera, C. R., Roche, T. E., Pelley, J. W., Randall, D. D.: Molecular aspects of the regulation of the mammalian pyruvate dehydrogenase. In: O. Wieland, E. Helmreich, H. Holzer (eds). 2nd Int. Sympos. Interconvertible Enzymes, Abstracts, pp. 28–29. Berlin-Heidelberg-New York: Springer 1971Google Scholar
  18. 18.
    Regen, D. M., Young, D. A. B., Davis, W. W., Jack, J., Jr., Park, C. R.: Adjustments of glycolysis to energy utilization in the perfused rat heart. The effects of changes in the ionic composition of the medium on phosphofructokinase activity. J. biol. Chem.239, 381–384 (1964)Google Scholar
  19. 19.
    Reinauer, H., Grassow, G., Hollmann, S.: Aktivitätsänderungen der Pyruvatdehydrogenase in Thiaminmangel. Hoppe-Seylers Z. physiol. Chem.349, 969–978 (1968)Google Scholar
  20. 20.
    Reinauer, H., Janssen, W., Hollmann, S.: Die Aktivität der 2-Oxosäure-Dehydrogenase bei Thiaminmangel der Ratte, mit einem Beitrag zur Aktivitätsmessung der Oxoglutarat-Dehydrogenase. Hoppe-Seylers Z. physiol. Chem.352, 125–131 (1971)Google Scholar
  21. 21.
    Reinauer, H., Müller-Ruchholtz, E. R.: Regulation of the pyruvate dehydrogenase complex in perfused hearts of guinea pigs. Hoppe-Seylers Z. physiol. Chem.355 (10), Short communications of the Joint Meeting 1974Google Scholar
  22. 22.
    Sarnoff, S. J., Braunwald, E., Welch, G. H., Jr., Case, R. B., Stainsby, W. N., Macruz, R.: Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time-index. Amer. J. Physiol.192, 148–156 (1958)Google Scholar
  23. 23.
    Schwartz, E., Reed, L.: Regulation of the activity of the PDH complex of E. coli. Biochem. biophys. Res. Commun.31, 495–500 (1968)Google Scholar
  24. 24.
    Siess, E. A., Wieland, O. H.: Purification and characterization of pyruvate dehydrogenase-phosphatase from pig heart muscle. Europ. J. Biochem.26, 96–105 (1972)Google Scholar
  25. 25.
    Siess, E., Wittmann, J., Wieland, O.: Interconversion and kinetic properties of PDH from brain. Hoppe-Seylers Z. physiol. Chem.352, 447–452 (1971)Google Scholar
  26. 26.
    Weiss, L., Löffler, G., Wieland, O. H.: Regulation by insulin of adipose tissue pyruvate dehydrogenase. Hoppe-Seylers Z. physiol. Chem.355, 363–377 (1974)Google Scholar
  27. 27.
    Wieland, O., v. Funcke, H., Löffler, G.: Interconversion of pyruvate dehydrogenase in rat heart muscle upon perfusion with fatty acids or ketone bodies. FEBS Letters15, 295–298 (1971)Google Scholar
  28. 28.
    Wieland, O., v. Jagow-Westermann, B., Stukowski, B.: Kinetic and regulatory properties of heart muscle pyruvate dehydrogenase. Hoppe-Seylers Z. physiol. Chem.350, 329–334 (1969)Google Scholar
  29. 29.
    Wieland, O., Siess, E., Schulze-Wethmar, F. H.: Der Einfluß von Hunger und Diabetes auf die Interkonvertierung von aktiver und inaktiver PDH verschiedener Rattenorganein vivo. Hoppe-Seylers Z. physiol. Chem.351, 1326–1327 (1970)Google Scholar
  30. 30.
    Williamson, I. R.: Metabolic control in the perfused rat heart. In: B. Chance, R. W. Estabrook, I. R. Williamson (eds.): Control of energy metabolism, pp. 333–346. New York: Academic Press 1965Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • Bernd Schulze Wischeler
    • 1
    • 2
  • Ernst R. Müller-Ruchholtz
    • 1
    • 2
  • H. Reinauer
    • 1
    • 2
  1. 1.Physiologisches Institut, Lehrstuhl I, der Universität DüsseldorfDüsseldorfDeutschland
  2. 2.Diabetes-Forschungsinstitut an der Universität DüsseldorfDüsseldorfDeutschland

Personalised recommendations