Abstract

The purpose of this study was to evaluate the consequences of non-linear changes in phosphocreatine (PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energy of ATP hydrolysis (delta GATP). Six subjects performed incremental plantar flexion exercise on a treadle ergometer while muscle P(i) metabolism (PCr, P(i), ATP) and pH were followed using 31P-nuclear magnetic resonance spectroscopy. Changes in ADP and delta GATP were estimated with the assumption that there was equilibrium of the creatine kinase reaction and homogeneous tissue metabolite pools. All six subjects showed a threshold for onset of cellular acidosis that occurred on average at 47.3 +/- 12.7% of peak work rate (PWR). In five of the six subjects, PCr and P(i) showed accelerated rates of change above the threshold for onset of cellular acidosis. In all six subjects, ADP, when correctly calculated considering changes in pH, rose in a curvilinear fashion that was well described by a Michaelis-Menten hyperbola through 60-100% of PWR, with a mean apparent Michaelis-Menten constant of 43.1 +/- 17.1 microM ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 +/- 94% of PWR. delta GATP rose linearly with work rate from -62.9 +/- 1.8 kJ/mol during unloaded treadling to -55.0 +/- 1.8 kJ/mol at PWR. If we assume a linear O2 uptake-to-work rate relationship, these results are most consistent with control of respiration being exerted through delta GATP under these conditions (incremental exercise by human calf muscle).(ABSTRACT TRUNCATED AT 250 WORDS)

Highlights

  • Physiol. 77(5):2169-2176,1994.-The PCr to change in work rate or change in PCr to change in purposeof this study wasto evaluate the consequencesof nonlinear changesin phosphocreatine(PCr) and pH during incremental calf exercise on estimates of ADP and cytosolic free energyof ATP hydrolysis (AG,)

  • All six subjects showed a threshold for onsetof cellular acidosisthat occurredon average at 47.3 t 12.7% of peak work rate (PWR)

  • (conditions reflecting metabolic rates ranging from rest MRS has been utilized during incremental exercise in through moderate-intensity exercise), the paradigms are human skeletal muscle, two responses have been reindistinguishable, i.e., a linear fall in PCr predicts a hy- ported that have not been clearly described in animal perbolic (Michaelis-Menten) rise in ADP and a linear muscle preparations: 1) there is a threshold work rate or rise in AGArp, when the Cr kinase (CK) reaction is as- metabolic rate for cellular acidosis and 2) above sumed to be at equilibrium

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Summary

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Connett and Honig [8] found that measured muscle Qo, was linearly related to both PCr and AGArp {as phosphor y 1at ion potential, In ([ATP] /[ADP] [Pi]), meanapparent Michaelis-Menten constant of 43.1 * 17.1PM where terms in brackets are concentrations} but not to ADP and a predicted maximal oxidative rate at PCr = 0, which was 241 t 94% of PWR. Kushmerick et al [15] showed that, in cat biceps but not soleus, changes in respiration could be explained metaboliccontrol; aerobicmetabolism;oxidative phosphoryla- by Michaelis-Menten changes in ADP. Both tion muscle. types showed relatively linear relationships between Qo, and PCr

Resolving this controversy in human muscle has been
OF SKELETAL
RESULTS
DISCUSSION
End Ex
Means t SD
CONTROL OF SKELETAL MUSCLE RESPIRATION
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