Factors determining the oxygen consumption rate (V.o2) on-kinetics in skeletal muscles

Abstract

Using a computer model of oxidative phosphorylation developed previously [Korzeniewski and Mazat (1996) Biochem. J. 319, 143-148; Korzeniewski and Zoladz (2001) Biophys. Chem. 92, 17-34], we analyse the effect of several factors on the oxygen-uptake kinetics, especially on the oxygen consumption rate (VO2) and half-transition time t(1/2), at the onset of exercise in skeletal muscles. Computer simulations demonstrate that an increase in the total creatine pool [PCr+/-Cr] (where Cr stands for creatine and PCr for phosphocreatine) and in glycolytic ATP supply lengthen the half-transition time, whereas increase in mitochondrial content, in parallel activation of ATP supply and ATP usage, in oxygen concentration, in proton leak, in resting energy demand, in resting cytosolic pH and in initial alkalization decrease this parameter. Theoretical studies show that a decrease in the activity of creatine kinase (CK) [displacement of this enzyme from equilibrium during on-transient (rest-to-work transition)] accelerates the first stage of the VO2 on-transient, but slows down the second stage of this transient. It is also demonstrated that a prior exercise terminated a few minutes before the principal exercise shortens the transition time. Finally, it is shown that at a given ATP demand, and under conditions where CK works near the thermodynamic equilibrium, the half-transition time of VO2 kinetics is determined by the amount of PCr that has to be transformed into Cr during rest-to-work transition; therefore any factor that diminishes the difference in [PCr] between rest and work at a given energy demand will accelerate the VO2 on-kinetics. Our conclusions agree with the general idea formulated originally by Easterby [(1981) Biochem. J. 199, 155-161] that changes in metabolite concentrations determine the transition times between different steady states in metabolic systems.

Regulation of oxidative phosphorylation through parallel activation

“…However, there is no direct evidence that such great diffusion gradients/displacement of CK from equilibrium take place in intact muscle where there is no unstirred layer, as in skinned fibers, and the creatine shuttle overcomes the possible ADP diffusion limitations. Computer simulations assuming the each-step-activation mechanism (Mechanism C), but not involving ADP diffusion gradients/CK disequilibrium are able to reproduce very well the kinetic behavior of oxidative phosphorylation in intact skeletal muscle [15,30] and heart [14,18]. It was demonstrated in the experimental way that in skeletal muscle with creatine kinase knockout it is ADP and not Cr that directly activates mitochondria [94].…”

“…These kinetic properties of the system can be accounted for by the discussed model of oxidative phosphorylation when it is assumed that the intensity of each-step activation is moderate-to-high in intact skeletal muscle stimulated neurally and low or zero in glycolytic skeletal muscle stimulated electrically [15]. The exponentiality of the time course of VO 2 and [PCr] at the onset of exercise is not trivial and is not predicted by the mechanistic-ultrasensitivity mechanism (Mechanism D) and CK-disequilibrium mechanism (Mechanism E), as discussed below and in [30].…”

“…The other Only a computer model that is very well tested by comparison with a possibly broad set of different parameter values and system properties encountered in experimental studies may be used for reliable theoretical studies on the modeled metabolic system and for predicting the existence of new phenomena. The discussed computer model has been extensively tested for a very broad set of different properties of the oxidative phosphorylation system [13][14][15][16][17][18][26][27][28][29][30]. The validation of the model concerns oxidative phosphorylation in isolated mitochondria, isolated hepatocytes, intact skeletal muscle and intact heart.…”

The Modeling of Oxidative Phosphorylation in Skeletal Muscle

“…Web site www.mol.uj.edu.pl/staff/benio has a complete description of the model. The discussed computer model has been extensively tested for a very broad set of different properties of the oxidative phosphorylation system [3][4][5][6][7][8].…”

Age‐ and sex‐related differences in muscle phosphocreatine and oxygenation kinetics during high‐intensity exercise in adolescents and adults

“…The [PCr] cost per watt was higher in females than males, and in children than adults, suggesting either a decreased oxidative capacity or an impaired exercise efficiency in these groups. Reduced mitochondrial content is associated with a greater PCr cost for an equivalent change in exercise intensity (41), which would suggest that mitochondrial capacity is lower in children compared with adults. This is contrary to previous reports of greater oxidative capacity in children (17,29), and suggestions that oxidative capacity might be higher in women than men (42).…”