Purpose: The biochemical background of the (near-)linear direct relationship between the curvature constant (W') of the power-duration curve and the magnitude ( ) of the slow component of the on-kinetics ( ) as well as reverse relationship between critical power (CP) and the characteristic transition time (t, analogous to τ) of the primary phase II of the on-kinetics encountered in experimental studies is studied.
Methods: A computer model of the bioenergetic system in skeletal muscle, involving the each-step-activation mechanism of work transitions and P double-threshold mechanism of muscle fatigue, is used.
Results: The activity (rate constant) (k) of the additional ATP usage, underlying the slow component, determines to a large extent the (near-)linear direct W'- relationship, as an increase in k increases markedly both W' and .
Eur J Appl Physiol
September 2024
Purpose: Endurance training improves running performance in distances where oxidative phosphorylation (OXPHOS) is the main ATP source. Here, a dynamic computer model is used to assess possible biochemical mechanisms underlying this improvement.
Methods: The dynamic computer model is based on the "P double-threshold" mechanism of muscle fatigue, according to which the additional ATP usage appears when (1) inorganic phosphate (P) exceeds a critical value (Pi); (2) exercise is terminated because of fatigue, when P reaches a peak value (Pi); (3) the P increase and additional ATP usage increase mutually stimulate each other.
Computer simulations using a dynamic model of the skeletal muscle bioenergetic system, involving the P-double-threshold mechanism of muscle fatigue, demonstrate that the training-induced increase in V·O, increase in critical power (CP) and acceleration of primary phase II of the V·O on kinetics (decrease in t) is caused by elevated OXPHOS activity acting through a decrease in and slowing of the P (inorganic phosphate) rise during the rest-to-work transition. This change leads to attenuation of the reaching by P of Pi, peak P at which exercise is terminated because of fatigue. The delayed (in time and in relation to V·O increase) P rise for a given power output (PO) in trained muscle causes P to reach Pi (in very heavy exercise) after a longer time and at a higher V·O; thus, exercise duration is lengthened, and V·O is elevated compared to untrained muscle.
View Article and Find Full Text PDFRespir Physiol Neurobiol
August 2023
Simulations using a computer model of the skeletal muscle bioenergetic system demonstrate that the slowed V̇O on-kinetics of the second step in two-step incremental exercise (exercise initiated from elevated baseline metabolic rate) can be accounted for by a decrease in the stimulation of oxidative phosphorylation (OXPHOS) and/or increase in the stimulation of glycolysis through each-step activation (ESA) in working skeletal muscle. This effect can be caused by either a recruitment of more glycolytic type IIa, IIx and IIb fibers or metabolic regulation in already recruited fibers, or both. The elevated-glycolysis-stimulation mechanism predicts that the end-second-step pH in two-step-incremental exercise is lower than the end-exercise pH in constant-power exercise with the same work intensity (power output).
View Article and Find Full Text PDFA computer model of the skeletal muscle bioenergetic system involving the P double-threshold mechanism of muscle fatigue was used to study the V̇O (non-)linear increase in time in ramp-incremental exercise as compared to the V̇O slow component in constant-power exercise. The P double-threshold mechanism applies to both constant-power and ramp-incremental exercise. The additional ATP usage is initiated at a significantly higher ATP usage activity (power output), determining the moderate/heavy exercise border, in ramp-incremental, than in constant-power exercise.
View Article and Find Full Text PDFRespir Physiol Neurobiol
January 2023
Relative sensitivities of the maximal oxygen uptake (V̇O), critical power (CP) and transition time of the primary phase II of the V̇O on-kinetics (t) to selected factors in skeletal muscle are simulated using a computer model of the skeletal muscle bioenergetic system. In normoxia, V̇O is significantly positively sensitive to peak P (P, P at which exercise is terminated because of fatigue), OXPHOS (oxidative phosphorylation) activity (k) and ESA (each-step-activation) intensity (A), and negatively sensitive to the accessible phosphate (and total creatine) pool (P). CP is additionally moderately positively sensitive to critical P (P, P at which the additional ATP usage appears) and negatively sensitive to the additional ATP usage activity (k).
View Article and Find Full Text PDFThis article presents the biochemical intra-skeletal-muscle basis of exercise intensity domains: moderate (M), heavy (H), very heavy (VH) and severe (S). Threshold origins are mediated by a 'Pi double-threshold' mechanism of muscle fatigue, which assumes (1) additional ATP usage, underlying muscle V̇O2 and metabolite slow components, is initiated when inorganic phosphate (Pi) exceeds a critical value (Picrit); (2) exercise is terminated because of fatigue, when Pi reaches a peak value (Pipeak); and (3) the Pi increase and additional ATP usage increase mutually stimulate each other forming a positive feedback. M/H and H/VH borders are defined by Pi on-kinetics in relation to Picrit and Pipeak.
View Article and Find Full Text PDFThe presented work's aim is the application of low-power laser treatment for the enhancement of interfacial micromechanical adhesion between polyamide 6 (filled with glass fiber) and aluminum. A fiber laser beam was used to prepare micro-patterns on aluminum sheets. The micro-structuring was conducted in the regime of 50, 100, 200 and 300 mm/s laser beam speeds, for both sides.
View Article and Find Full Text PDFRespir Physiol Neurobiol
February 2022
A computer model of the skeletal muscle bioenergetic system, involving the "P double-threshold" mechanism of muscle fatigue, was used to investigate the effect of muscle training on system kinetic properties in mitochondrial myopathies (MM) patients with inborn OXPHOS deficiencies. An increase in OXPHOS activity and decrease in peak P can account for the training-induced increase in V̇O, acceleration of the primary phase II of the V̇O on-kinetics, delay of muscle fatigue and prolongation of exercise at a given work intensity encountered in experimental studies. Depending on the mutation load and work intensity, training can bring the muscle from severe- to very-heavy- to moderate-exercise-like behavior, thus lessening the exertional fatigue and lengthening the physical activity of a given intensity.
View Article and Find Full Text PDFSimulations carried out using a previously developed model of the skeletal muscle bioenergetic system, involving the "inorganic phosphate (P) double-threshold" mechanism of muscle fatigue, lead to the conclusion that a decrease in the oxidative phosphorylation (OXPHOS) activity, caused by mutations in mitochondrial or nuclear DNA, is the main mechanism underlying the changes in the kinetic properties of the system in mitochondrial myopathies (MM). These changes generally involve the very-heavy-exercise-like behavior and exercise termination because of fatigue at low work intensities. In particular, a sufficiently large (at a given work intensity) decrease in OXPHOS activity leads to slowing of the primary phase II of the oxygen uptake (V̇o) on-kinetics, decrease in maximal V̇o (V̇o), appearance of the slow component of the V̇o on-kinetics, exercise intolerance, and lactic acidosis at relatively low power outputs encountered in experimental studies in patients with MM.
View Article and Find Full Text PDFJ Appl Physiol (1985)
February 2021
Computer simulations, using the "P double-threshold" mechanism of muscle fatigue postulated previously (the first threshold initiating progressive reduction in work efficiency and the second threshold resulting in exercise intolerance), demonstrated that several parameters of the skeletal muscle bioenergetic system can affect maximum oxygen consumption (V̇O), critical power (CP), and oxygen consumption (V̇O) on-kinetics in skeletal muscle. Simulations and experimental observations together demonstrate that endurance exercise training increases oxidative phosphorylation (OXPHOS) activity and/or each-step activation (ESA) intensity, the latter, especially in the early stages of training. Here, new computer simulations demonstrate that an endurance training-induced increase in OXPHOS activity and decrease in peak P (Pi), at which exercise is terminated because of exercise intolerance, result in increased V̇O and CP, speeding of the primary phase II of V̇O on-kinetics, and decreases V̇O slow component magnitude, consistent with their observed behavior in vivo.
View Article and Find Full Text PDFPurpose: The consequences of the assumption that the additional ATP usage, underlying the slow component of oxygen consumption ([Formula: see text]) and metabolite on-kinetics, starts when cytosolic inorganic phosphate (P) exceeds a certain "critical" P concentration, and muscle work terminates because of fatigue when P exceeds a certain, higher, "peak" P concentration are investigated.
Methods: A previously developed computer model of the myocyte bioenergetic system is used.
Results: Simulated time courses of muscle [Formula: see text], cytosolic ADP, pH, PCr and P at various ATP usage activities agreed well with experimental data.
Eur J Appl Physiol
October 2019
Purpose: Consequences of combining three ideas proposed previously by other authors: (1) that there exists a critical power (CP), above which no steady state in [Formula: see text]O (oxygen consumption) and metabolites can be achieved in voluntary constant-power exercise; (2) that muscle fatigue is related to decreased exercise efficiency (increased [Formula: see text]O/power output ratio); and (3) that P (inorganic phosphate) is the main fatigue-related metabolite are investigated.
Methods: A previously-developed computer model of the skeletal muscle bioenergetic system is used. It was assumed in computer simulations that skeletal muscle work terminates when cytosolic P (inorganic phosphate) exceeds a certain critical level.
The time constant of the primary phase of pulmonary V˙O on-kinetics (τ ), which reflects muscle V˙O kinetics during moderate-intensity exercise, is about 30 s in young healthy untrained individuals, while it can be as low as 8 s in endurance-trained athletes. We aimed to determine the intramuscular factors that enable very low values of t to be achieved (analogous to τ , t is the time to reach 63% of the V˙O amplitude). A computer model of oxidative phosphorylation (OXPHOS) in skeletal muscle was used.
View Article and Find Full Text PDFA computer model of the skeletal muscle bioenergetic system was used to study the regulation of oxidative phosphorylation (OXPHOS) in electrically-stimulated and cortically-stimulated skeletal muscle. Two types of the dependence of the intensity of each-step activation (ESA) of OXPHOS complexes on ATP usage activity were tested: power-type dependence and saturating-type dependence. The dependence of muscle oxygen consumption ([Formula: see text]), phosphocreatine (PCr), cytosolic ADP, ATP, inorganic phosphate (Pi), pH and τp (characteristic transition time) of the principal component of the muscle [Formula: see text] on-kinetics on the ATP usage activity was simulated for both types of the ESA intensity-ATP usage activity dependence.
View Article and Find Full Text PDFA computer model was used to simulate the dependence of protonmotive force (Δp), proton leak and phenomenological (involving proton leak) ATP/O2 ratio on work intensity in skeletal muscle. Δp, NADH and proton leak decreased with work intensity. The contribution of proton leak to oxygen consumption ([Formula: see text]) decreased from about 60% at rest to about 3 and 1% at moderate and heavy/severe exercise, respectively, while the ATP/O2 ratio increased from 2.
View Article and Find Full Text PDFThe mechanisms responsible for matching of the highly varying ATP demand by ATP supply in muscle are of primary importance for pure science, sport science and medicine. According to the traditional opinion ATP supply is activated by elevated ADP and P resulting from ATP hydrolysis during intensive work. Theoretical studies using the computer model of oxidative phosphorylation (OXPHOS) and the entire cell bioenergetic system developed by the author and co-workers lead to the each-step-activation (ESA) mechanism of the regulation of the system in skeletal muscle, heart and other tissues during work transitions.
View Article and Find Full Text PDFA model of the cell bioenergetic system was used to compare the effect of oxidative phosphorylation (OXPHOS) deficiencies in a broad range of moderate ATP demand in skeletal muscle and heart. Computer simulations revealed that kinetic properties of the system are similar in both cases despite the much higher mitochondria content and "basic" OXPHOS activity in heart than in skeletal muscle, because of a much higher each-step activation (ESA) of OXPHOS in skeletal muscle than in heart. Large OXPHOS deficiencies lead in both tissues to a significant decrease in oxygen consumption (V̇o2) and phosphocreatine (PCr) and increase in cytosolic ADP, Pi, and H(+) The main difference between skeletal muscle and heart is a much higher cytosolic Pi concentration in healthy tissue and much higher cytosolic Pi accumulation (level) at low OXPHOS activities in the former, caused by a higher PCr level in healthy tissue (and higher total phosphate pool) and smaller Pi redistribution between cytosol and mitochondria at OXPHOS deficiency.
View Article and Find Full Text PDFIn this study we have examined the effect of prolonged endurance training program on the pulmonary oxygen uptake (V'O2) kinetics during heavy-intensity cycling-exercise and its impact on maximal cycling and running performance. Twelve healthy, physically active men (mean±SD: age 22.33±1.
View Article and Find Full Text PDFKey Points: The basic control mechanisms of oxidative phosphorylation (OXPHOS) and glycolysis during work transitions in human skeletal muscle are still a matter of debate. We used simulations of skeletal muscle bioenergetics to identify key system features that contribute to this debate, by comparing kinetic model outputs with experimental human data, including phosphocreatine, pH, pulmonary oxygen uptake and fluxes of ATP production by OXPHOS (vOX), anaerobic glycolysis and creatine kinase in moderate and severe intensity exercise transitions. We found that each-step activation of particular OXPHOS complexes, NADH supply and glycolysis, and strong (third-order) glycolytic inhibition by protons was required to reproduce observed phosphocreatine, pH and vOX kinetics during exercise.
View Article and Find Full Text PDFThe effects of inborn oxidative phosphorylation (OXPHOS) complex deficiencies or possible each-step activation (ESA) dysfunction on the bioenergetic system in working intact skeletal muscle are studied using a computer model of OXPHOS published previously. The curves representing the dependencies of V˙O2 and metabolite concentrations on single complex activity, entire OXPHOS activity or ESA intensity exhibit a characteristic threshold at some OXPHOS complex activity/ESA intensity. This threshold for V˙O2 of single complex activities is significantly lower in intact muscle during moderate and heavy work, than in isolated mitochondria in state 3.
View Article and Find Full Text PDFJ Appl Physiol (1985)
May 2015
A computer model of a skeletal muscle bioenergetic system is used to study the background of the slow component of oxygen consumption V̇O2 on-kinetics in skeletal muscle. Two possible mechanisms are analyzed: inhibition of ATP production by anaerobic glycolysis by progressive cytosol acidification (together with a slow decrease in ATP supply by creatine kinase) and gradual increase of ATP usage during exercise of constant power output. It is demonstrated that the former novel mechanism is potent to generate the slow component.
View Article and Find Full Text PDFA computer model of oxidative phosphorylation (OXPHOS) in skeletal muscle is used to compare state 3, intermediate state and state 4 in mitochondria with rest and work in skeletal muscle. 'Idealized' state 4 and 3 in relation to various 'experimental' states 4 and 3 are defined. Theoretical simulations show, in accordance with experimental data, that oxygen consumption (V'O2), ADP and Pi are higher, while ATP/ADP and Δp are lower in rest than in state 4, because of the presence of basal ATP consuming reactions in the former.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
November 2014
The effect of prolonged endurance training on the pulmonary V̇O2 on- and off-kinetics in humans, in relation to muscle mitochondria biogenesis, is investigated. Eleven untrained physically active men (means±SD: age 22.4±1.
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