Skip to main content
SpringerLink
Log in

Tricarboxylic acid cycle intermediates accumulate at the onset of intense exercise in man but are not essential for the increase in muscle oxygen uptake

  • Skeletal Muscle
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

It was proposed that a contraction-induced increase in tricarboxylic acid cycle intermediates (TCAI) is obligatory for the increase in muscle oxygen uptake at the start of exercise. To test this hypothesis, we measured changes in muscle TCAI during the initial seconds of intense exercise and used dichloroacetate (DCA) in an attempt to alter the level of TCAI. Five men performed strenuous leg kicking exercise (64±8 W) under noninfused control (CON) and DCA-supplemented conditions; biopsies (vastus lateralis) were obtained at rest and after 5, 15, and 180 s of exercise. In CON, the total concentration of three measured TCAI (ΣTCAI: citrate, malate, and fumarate) increased (p<0.05) by 71% during the first 15 s of exercise. The ΣTCAI was lower (p<0.05) in DCA than in CON at rest [0.18±0.02 vs 0.64±0.09 mmol kg−1 dry weight (d.w.)], after 5 s (0.30±0.07 vs 0.85±0.14 mmol kg−1 d.w.), and 15 s of exercise (0.60±0.07 vs 1.09±0.16 mmol kg−1 d.w.), but not different after 3 min (3.12±0.53 vs 3.23±0.55 mmol kg−1 d.w.). Despite differences in the level of muscle TCAI, muscle phosphocreatine degradation was similar in DCA and CON during the first 15 s of exercise (17.5±3.3 vs 25.6±4.1 mmol kg−1 d.w.). Taken together with our previous observation that DCA does not alter muscle oxygen uptake during the initial phase of intense leg kicking exercise (Bangsbo et al. Am J Physiol 282:R273–R280, 2002), the present data suggest that muscle TCAI accumulate during the initial seconds of exercise; however, this increase is not essential for the contraction-induced increase in mitochondrial respiration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Andersen P, Adams RP, Sjøgaard G, Thorboe A, Saltin B (1985) Dynamic knee extension as a model for the study of an isolated exercising muscle in man. J Appl Physiol 59:1647–1653

    PubMed  CAS  Google Scholar 

  2. Bangsbo J, Gollnick PD, Graham TE, Juel C, Kiens B, Mizuno M, Saltin B (1990) Anaerobic energy production and O2 deficit–debt relationship during exhaustive exercise in humans. J Physiol 422:539–559

    PubMed  CAS  Google Scholar 

  3. Bangsbo J, Krustrup P, González-Alonso J, Saltin B (2000) Muscle oxygen kinetics at onset of intense dynamic exercise in humans. Am J Physiol 279(3):R899–R906

    CAS  Google Scholar 

  4. Bangsbo J, Krustrup P, González-Alonso J, Saltin B (2001) ATP production and mechanical efficiency of human skeletal muscle during intense exercise: effect of previous exercise. Am J Physiol 280:E956–E964

    CAS  Google Scholar 

  5. Bangsbo J, Gibala M, Krustrup P, González-Alonso J, Saltin B (2002) Enhanced pyruvate dehydrogenase activity does not affect muscle O2 uptake at onset of intense exercise in humans. Am J Physiol 282:R273–R280

    CAS  Google Scholar 

  6. Bergmeyer HU (1974) Methods of enzymatic analysis, 2nd edn. Academic, New York

    Google Scholar 

  7. Bergström J (1962) Muscle electrolytes in man. Scand J Clin Lab Invest Suppl 68:1–101

    Google Scholar 

  8. Chung Y, Mole PA, Sailasuta N, Tran TK, Hurd R, Jue T (2005) Control of respiration and bioenergetics during muscle contraction. Am J Physiol 288(3):C730–C738

    Article  CAS  Google Scholar 

  9. Constantin-Teodosiu D, Simpson EJ, Greenhaff PL (1998) Effects of pyruvate, dichloroacetate and adrenaline infusion on pyruvate dehydrogenase complex activation and tricarboxylic acid cycle intermediates in human skeletal muscle. J Physiol 506:102P

    Google Scholar 

  10. Dawson KD, Howarth KR, Tarnopolsky MA, Wong ND, Gibala MJ (2003) Short-term training attenuates muscle TCA cycle expansion during exercise in women. J Appl Physiol 95(3):999–1004

    PubMed  CAS  Google Scholar 

  11. Dawson KD, Baker DJ, Greenhaff PL, Gibala MJ (2005) An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle. J Physiol 565(2):637–643

    Article  PubMed  CAS  Google Scholar 

  12. Gibala MJ, Saltin B (1999) PDH activation by dichloroacetate reduces TCA cycle intermediates at rest but not during exercise in humans. Am J Physiol 277(1):E33–E38

    PubMed  CAS  Google Scholar 

  13. Gibala MJ, Tarnopolsky MA, Graham TE (1997) Tricarboxylic acid cycle intermediates in human muscle at rest and during prolonged cycling. Am J Physiol 272(1):E239–E244

    PubMed  CAS  Google Scholar 

  14. Gibala MJ, MacLean DA, Graham T, Saltin B (1998) Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am J Physiol 275(2):E235–E242

    PubMed  CAS  Google Scholar 

  15. Gibala MJ, Young ME, Taegtmeyer H (2000) Anaplerosis of the citric acid cycle: role in energy metabolism of heart and skeletal muscle. Acta Physiol Scand 168(4):657–665

    Article  PubMed  CAS  Google Scholar 

  16. Gibala MJ, González-Alonso J, Saltin B (2002) Dissociation between muscle tricarboxylic acid cycle pool size and aerobic energy provision during prolonged exercise in humans. J Physiol 545(2):705–713

    Article  PubMed  CAS  Google Scholar 

  17. Grassi B (2000) Skeletal muscle VO2 on-kinetics: set by O2 delivery or by O2 utilization? New insights into an old issue. Med Sci Sports Exerc 32(1):108–116

    Article  PubMed  CAS  Google Scholar 

  18. Grassi B, Poole DC, Richardson RS, Knight DR, Erickson BK, Wagner PD (1996) Muscle O2 uptake kinetics in humans: implications for metabolic control. J Appl Physiol 80:988–998

    PubMed  CAS  Google Scholar 

  19. Grassi B, Gladden LB, Samaja M, Stary CM, Hogan MC (1998) Faster adjustment of O2 delivery does not affect VO2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85(4):1394–1403

    PubMed  CAS  Google Scholar 

  20. Grassi B, Gladden LB, Stary CM, Wagner PD, Hogan MC (1998) Peripheral O2 diffusion does not affect VO2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85(4):1404–1412

    PubMed  CAS  Google Scholar 

  21. Harris RC, Hultman E, Nordesjö O (1974) Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Scand J Clin Lab Invest 33:109–120

    Article  PubMed  CAS  Google Scholar 

  22. Howarth KR, LeBlanc PJ, Heigenhauser GJ, Gibala MJ (2004) Effect of endurance training on muscle TCA cycle metabolism during exercise in humans. J Appl Physiol 97(2):579–584

    Article  PubMed  CAS  Google Scholar 

  23. Howlett RA, Heigenhauser GJ, Spriet LL (1999) Skeletal muscle metabolism during high-intensity sprint exercise is unaffected by dichloroacetate or acetate infusion. J Appl Physiol 87(5):1747–1751

    PubMed  CAS  Google Scholar 

  24. Hughson RL, Shoemaker JK, Tschakovsky ME, Kowalchuk (1996) Dependence of muscle VO2 on blood flow of forearm exercise. J Appl Physiol 81(4):1516–1521

    PubMed  Google Scholar 

  25. Hughson RL, Tschakovsky ME, Houston ME (2001) Regulation of oxygen consumption at the onset of exercise. Exerc Sport Sci Rev 29(3):129–133

    Article  PubMed  CAS  Google Scholar 

  26. Korzeniewski B, Zoladz JA (2004) Factors determining the oxygen consumption rate (VO2) on-kinetics in skeletal muscles. Biochem J 379(3):703–710

    Article  PubMed  CAS  Google Scholar 

  27. Krustrup P, González-Alonso J, Quistorff B, Bangsbo J (2001) Muscle heat production and anaerobic energy turnover during repeated intense dynamic exercise in humans. J Physiol 536:947–956

    Article  PubMed  CAS  Google Scholar 

  28. Krustrup P, Hellsten Y, Bangsbo J (2004) Intense interval training enhances human skeletal muscle oxygen uptake in the initial phase of dynamic exercise at high but not at low intensities. J Physiol 559(1):335–345

    Article  PubMed  CAS  Google Scholar 

  29. Lee SH, Davis EJ (1979) Carboxylation and decarboxylation reactions. Anaplerotic flux and removal of citrate cycle intermediates in skeletal muscle. J Biol Chem 254(2):420–430

    PubMed  CAS  Google Scholar 

  30. Ludvik B, Mayer G, Stifter S, Putz D, Barnas U, Graf H (1993) Effects of dichloroacetate on exercise performance in healthy volunteers. Pflugers Arch 423(3–4):251–254

    Article  PubMed  CAS  Google Scholar 

  31. Messer JI, Jackman MR, Willis WT (2004) Pyruvate and citric acid cycle carbon requirements in isolated skeletal muscle mitochondria. Am J Physiol 286:C565–C572

    Article  CAS  Google Scholar 

  32. Molé PA, Chung Y, Tran TK, Sailasuta N, Hurd R, Jue T (1999) Myoglobin desaturation with exercise intensity in human gastrocnemius muscle. Am J Physiol 277(1):R173–R180

    PubMed  Google Scholar 

  33. Passonneau JV, Lowry OH (1993) Enzymatic analysis: a practical guide. Humana Press, Totowa, NJ

    Google Scholar 

  34. Sahlin K, Katz A, Broberg S (1990) Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. Am J Physiol 259:C834–C841

    PubMed  CAS  Google Scholar 

  35. Stacpoole PW (1989) The pharmacology of dichloroacetate. Metabolism 38(11):1124–1144

    Article  PubMed  CAS  Google Scholar 

  36. Timmons JA, Gustafsson T, Sundberg CJ, Jansson E, Greenhaff PL (1998) Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise. Am J Physiol 274:E377–E380

    PubMed  CAS  Google Scholar 

  37. Timmons JA, Poucher SM, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL (1998) Regulation of skeletal muscle carbohydrate oxidation during steady-state contraction. Am J Physiol 274:R1384–R1389

    PubMed  CAS  Google Scholar 

  38. Vicini P, Kushmerick MJ (2000) Cellular energetics analysis by a mathematical model of energy balance: estimation of parameters in human skeletal muscle. Am J Physiol 279(1):C213–C224

    CAS  Google Scholar 

  39. Walsh B, Tonkonogi M, Söderlund K, Hultman E, Saks V, Sahlin K (2001) The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle. J Physiol 537(3):971–978

    Article  PubMed  CAS  Google Scholar 

  40. Williamson JR, Cooper RH (1980) Regulation of the citric acid cycle in mammalian systems. FEBS Lett 117:K73–K83 (Suppl)

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the subjects for their committed participation. We also thank Merete Vannby and Ingelise Kring for excellent technical assistance. The study was supported by a grant from The Danish National Research Foundation (504-14). In addition, support was obtained from Team Denmark and The Natural Sciences and Engineering Research Council of Canada.

Author information

Authors and Affiliations

  1. Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark

    Jens Bangsbo & Peter Krustrup

  2. Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada

    Martin J. Gibala & Krista R. Howarth

  3. The August Krogh Institute, LHF, Universitetsparken 13, Copenhagen Ø, 2100, Denmark

    Jens Bangsbo

Authors
  1. Jens Bangsbo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin J. Gibala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Krista R. Howarth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Krustrup
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jens Bangsbo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bangsbo, J., Gibala, M.J., Howarth, K.R. et al. Tricarboxylic acid cycle intermediates accumulate at the onset of intense exercise in man but are not essential for the increase in muscle oxygen uptake. Pflugers Arch - Eur J Physiol 452, 737–743 (2006). https://doi.org/10.1007/s00424-006-0075-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-006-0075-4

Keywords

Search

Navigation