Abstract
Borrowing from metabolic control analysis the concept of control coefficients or c i values, defined as fractional change in MMR/fractional change in the capacity of any given step in ATP turnover, we used four performance phenotypes to compare mechanisms of control of aerobic maximum metabolic rate (MMR): (i)) untrained sedentary (US) subjects, as a reference group against which to compare (ii) power trained (PT), (iii) endurance trained (ET), and (iv) high altitude adapted native (HA) subject groups. Sprinters represented the PT group; long distance runners illustrated the ET group; and Andean natives represented the HA group. Numerous recent studies have identified contributors to control on both the adenosine triphosphate (ATP) supply side and the ATP demand side of ATP turnover. From the best available evidence it appears that at MMR all five of the major steps in energy delivery (namely, ventilation, pulmonary diffusion, cardiac output, tissue capillary – mitochondrial O2 transfer, and aerobic cell metabolism per se) approach an upper functional ceiling, with control strength being distributed amongst the various O2 flux steps. On the energy demand side, the situation is somewhat simplified since at MMR ∽ 90% of O2-based ATP synthesis is used for actomyosin (AM) and Ca2+ ATPases; at MMR these two ATP demand rates also appear to be near an upper functional ceiling. In consequence, at MMR the control contributions or c i values are distributed amongst all seven major steps in ATP supply and ATP demand pathways right to the point of fatigue. Relative to US (the reference group), in PT subjects at MMR control strength shifts towards O2 delivery steps (ventilation, pulmonary diffusion, and cardiac output); here physiological regulation clearly dominates MMR control. In contrast in ET and HA subjects at MMR control shifts towards the energy demand steps (AM and Ca2+ ATPases), and more control strength is focussed on tissue level ATP supply and ATP demand. One obvious advantage of the ET and HA biochemical-level control is improved metabolite homeostasis. Additionally, with some reserve capacity in the O2 delivery steps, the focussing of control on ATP turnover at the tissue level has allowed nature to improve on an ‘endurance machine’ design.
Similar content being viewed by others
Reference
Allen PS, Matheson GO, Zhu G, Gheorgiu D, Dunlop RS, Falconer T, Stanley C, Hochachka PW: Simultaneous 31P MRS of the soleus and gastrocnemius in Sherpas during graded calf muscle exercise. Am J Physiol 273: R999–R1007, 1997
Arthur PG, Hogan MC, Bebout DE, Wagner PD, Hochachka PW: Modeling the effects of hypoxia on ATP turnover in exercising muscle. J Appl Physiol 73: 737–742, 1992
Bassett DR Jr, Howley ET: Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med Sci Sports Exerc 32: 70–84, 2000
Bishop CM: The maximum oxygen consumption and aerobic scope of birds and mammals: getting to the heart of the matter. Proc R Soc Lond B Biol Sci 266: 2275–2281, 1999
Brooks GA, Fahey TD, White TP, Baldwin KM: In: Exercise Physiology: Human Bioenergetics and its Applications. Mayfield Publishing Co., Mountain View, CA, 2000
Cerretelli P, Kayser B, Hoppeler H, Pette D: Muscle morphometry and enzymes with acclimatization. In: J.R. Sutton, J.E. Remmers (eds). Hypoxia: The Adaptations. B.C. Deckers Inc., Toronto/Philadelphia, 1990, pp 220–224
Darveau CA, Hochacka PW: Allometric cascade: A model for resolving the problem of body mass effects on physiology and metabolism. Comp Biochem Physiol (in press)
Darveau CA, Suarez RK, Andrews RD, Hochachka PW: Allometric cascade as a unifying principle of body mass effects on metabolism. Nature 417: 166–170, 2002
Dawson B, Fitzsimons M, Green S, Goodman C, Carey M, Cole K: Changes in performance, muscle metabolites, enzymes and fibre types after short sprint training. Eur J Appl Physiol Occup Physiol 78: 163–169, 1998
di Prampero PE. Metabolic and circulatory limitations to VO2max at the whole animal level. J Exp Biol 115: 319–331, 1985
Fell DA, Thomas S: Physiological control of metabolic flux: The requirement for multisite modulation. Biochem J 311: 35–39, 1995
Green H, Grant S, Bombardier E, Ranney D: Initial aerobic power does not alter muscle metabolic adaptations to short-term training. Am J Physiol 277: E39–E48, 1999
Hochachka PW: In: Muscles as Molecular and Metabolic Machines. CRC Press, Boca Raton, Florida, 1994
Hochachka PW, Beatty CL, Burelle Y, Trump ME, McKenzie DC, Matheson GO: The lactate paradox in human high-altitude physiological performance. News Physiol Sci 17: 122–126, 2002
Hochachka PW, Bianconcini MS, Parkhouse WS, Dobson GP: On the role of actomyosin ATPases in regulation of ATP turnover rates during intense exercise. Proc Natl Acad Sci USA 88: 5764–5768, 1991
Hochachka PW, Clark CM, Holden JE, Stanley C, Ugurbil K, Menon RS: 31P magnetic resonance spectroscopy of the Sherpa heart: A phosphocreatine/adenosine triphosphate signature of metabolic defense against hypobaric hypoxia. Proc Natl Acad Sci USA 93: 1215–1220, 1996
Hochachka PW, Rupert JL, Monge C: Adaptation and conservation of physiological systems in the evolution of human hypoxia tolerance. Comp Biochem Physiol A Mol Integr Physiol 124: 1–17, 1999
Hochachka PW, Somero G.N: Biochemical Adaptation — Mechanism and Process in Physiological Evolution. Oxford Press, New York, 2002
Hochachka PW, Stanley C, Matheson GO, McKenzie DC, Allen PS, Parkhouse WS: Metabolic and work efficiencies during exercise in Andean natives. J Appl Physiol 70: 1720–1730, 1991
Jeneson JA, Westerhoff HV, Kushmerick MJ: A metabolic control analysis of kinetic controls in ATP free energy metabolism in contracting skeletal muscle. Am J Physiol Cell Physiol 279: C813–C832, 2000
Jones JH: Optimization of the mammalian respiratory system: Symmorphosis vs. single species adaptation. Comp Biochem Physiol B Biochem Mol Biol 120: 125–138, 1998
Jones RL, Man SF, Matheson GO, Parkhouse WS, Allen PS, McKenzie DC, Hochachka PW: Overall and regional lung function in Andean natives after descent to low altitude. Respir Physiol 87: 11–24, 1992
Kacser H, Burns JA: The control of flux. Biochem Soc Trans 23: 341–366, 1995
Kacser H, Burns JA: Molecular democracy: Who shares the controls? Biochem Soc Trans 7: 1149–1160, 1979
Kleiber M: Body size and metabolism. Hilgarida 6: 315–353, 1932
Korzeniewski B: Regulation of ATP supply in mammalian skeletal muscle during resting state — intensive work transition. Biophys Chem 83: 19–34, 2000
Linossier MT, Dormois D, Perier C, Frey J, Geyssant A, Denis C: Enzyme adaptations of human skeletal muscle during bicycle short-sprint training and detraining. Acta Physiol Scand 161: 439–445, 1997
MacDougall JD, Hicks AL, MacDonald JR, McKelvie RS, Green HJ, Smith KM: Muscle performance and enzymatic adaptations to sprint interval training. J Appl Physiol 84: 2138–2142, 1998
Matheson GO, Allen PS, Ellinger DC, Hanstock CC, Gheorghiu D, McKenzie DC, Stanley C, Parkhouse WS, Hochachka PW: Skeletal muscle metabolism and work capacity: A 31P-NMR study of Andean natives and lowlanders. J Appl Physiol 70: 1963–1976, 1991
Maurer J, Konstanczak P, Sollner O, Ehrenstein T, Knollmann F, Wolff R, Vogl TJ, Felix R: Muscle metabolism of professional athletes using 31P-spectroscopy. Acta Radiol 40: 73–77, 1999
McKenna MJ, Heigenhauser GJ, McKelvie RS, Obminski G, MacDougall JD, Jones NL: Enhanced pulmonary and active skeletal muscle gas exchange during intense exercise after sprint training in men. J Physiol 501: 703–716, 1997
Nogueira V, Rigoulet M, Piquet MA, Devin A, Fontaine E, Leverve XM: Mitochondrial respiratory chain adjustment to cellular energy demand. J Biol Chem 276: 46104–46110, 2001
Pedemonte M, Sandri C, Schiaffino S, Minetti C: Early decrease of IIx myosin heavy chain transcripts in Duchenne muscular dystrophy. Biochem Biophys Res Commun 255: 466–469, 1999
Rolfe DF, Brown GC: Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77: 731–758, 1997
Rubner M: Ueber den einfluss der korpergrosse aug stoff and kraftwechsel. Z Biol 19: 535–562, 1883
Sheel AW, McKenzie DC: Hypoxemia during exercise in health and disease. Clin Exerc Physiol 2: 116–127, 2000
Suarez RK, Staples JF, Lighton JR, West TG: Relationships between enzymatic flux capacities and metabolic flux rates: Nonequilibrium reactions in muscle glycolysis. Proc Natl Acad Sci USA 94: 7065–7069, 1997
Szentesi P, Zaremba R, van Mechelen W, Stienen GJ: ATP utilization for calcium uptake and force production in different types of human skeletal muscle fibres. J Physiol 531: 393–403, 2001
ter Kuile BH, Westerhoff HV: Transcriptome meets metabolome: Hierarchical and metabolic regulation of the glycolytic pathway. FEBS Lett 500: 169–171, 2001
Tesch PA, Karlsson J: Muscle fiber types and size in trained and untrained muscles of elite athletes. J Appl Physiol 59: 1716–1720, 1985
Thomas S, Fell DA: A control analysis exploration of the role of ATP utilisation in glycolytic-flux control and glycolytic-metabolite-concentration regulation. Eur J Biochem 258: 956–967, 1998
Trump ME, Hanstock CC, Allen PS, Gheorghiu D, Hochachka PW: An (1)H-MRS evaluation of the phosphocreatine/creatine pool (tCr) in human muscle. Am J Physiol Regul Integr Comp Physiol 280: R889–R896, 2001
Voit E: Computational Analysis of Biochemical Systems. Cambridge University Press, Cambridge, UK, 2000
Wagner PD: Algebraic analysis of the determinants of VO2max. Respir Physiol 93: 221–237, 1993
Weibel ER: Symmorphosis, On Form and Function Shaping Life. Harvard University Press, Cambridge, MA, 2000
Westerblad H, Allen DG, Lannergren J: Muscle fatigue: Lactic acid or inorganic phosphate the major cause? News Physiol Sci 17: 17–21, 2002
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hochachka, P.W., Burelle, Y. Control of maximum metabolic rate in humans: Dependence on performance phenotypes. Mol Cell Biochem 256, 95–103 (2004). https://doi.org/10.1023/B:MCBI.0000009861.45692.ed
Issue Date:
DOI: https://doi.org/10.1023/B:MCBI.0000009861.45692.ed