Acid, the Enemy of the Quick
High lactic acid concentration is the main factor limiting muscular contraction. (Meerson, 1973, 1986)
“Acidosis…leads to disruption of nerve cells’ activity and a development of defensive inhibition in them, worsening of excitation transmission from the nerve to the muscle.” Na+-K+ pumps’ conductivity to ions is reduced. (Volkov et al., 2000)
H+ inhibits ATPase, both in myosin and calcium pumps, thus compromising both contraction and relaxation. (Mikhailov, 2002)
H+ interferes with Ca2+ reaching the troponin/tropomyosin complex. (Brooks & Fahey, 2004)
H+ depresses Ca2+ reuptake into the sarcoplasmic reticula.
H+ inhibits CK, glycolytic, and aerobic enzymes.
H+ uncouples oxidation and phosphorylation in the mitochondria. (Volkov et al., 2000)
“Muscle contractility includes parameters such as maximal force, shortening velocity, and a rate of relaxation…Since the power output is the product of force and velocity, a decrease of 20 percent of each of these factors reduces power by almost 40 percent.” (Hargreaves & Spriet, 2006)
Correlation between lactate concentration in the working muscles and the power output decrease graph is based on Volkov et al. (2000).
In maximal veloergometer exercise power drops by up to 40–50 percent by 30 seconds. (Nevill et al., 1996)
In the state of fatigue, especially in cyclical work, the muscles no longer able to exert quick,powerful efforts compensate with longer and weaker contractions. (Farfel, 1972; Kourakin,1972; Volkov et al., 1974) The resulting changes in proprioception and unfavorable metabolic changes lead to a disintegration of the optimal relationships between somatic, vegetative, and other systems, movement discoordination, and a sharp reduction in the working effect of the movement. (Mogendovich, 1963; Mouravov et al., 1984; cited by Verkhoshansky, 1988)
Study of the anabolic and catabolic effects of different types of exercises and loads in female speedskaters. (Erkomayshvili, 1990)
Quote. (Selouyanov, 2013)
An increase of H+ concentration in the sarcoplasm facilitates the peroxidation reaction. (Hochachka & Somero, 1988) Lower pH makes low activity free radicals convert into more aggressive species. (Hess et al., 1982, etc.)
In physiologic quantities ROS have a hormetic effect (Yakovlev, 1983): Stimulate synthesis of protective proteins and increases the organism’s resistance to stress, exercise, cold, diets rich in oxidative substrates, hypoxia, etc. (Sazontova & Arkhipenko, 2004)
“The most important physiological functions of ROS include (i) oxidation and utilization of damaged molecules; (ii) synthesis of messenger molecules, and (iii) participation in redox signaling pathways and intracellular transfer of external signals to cell nuclei terminated by protein synthesis…” (Arkhipenko et al., 2014)
Physiologic concentrations of ROS are essential for initiating mitochondrial biogenesis.(Paulsen et al., 2014) It has been suggested that the expression of PGC-1α requires an optimal concentration of ROS. (Lira et al., 2010)
There is “a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise.” (Sastre et al., 1992) GSH is an antioxidant. An increase in the levels of its oxidized version, GSSG, indicates oxidative stress.
The simplified chart in the text, “Linear relationship between lactate concentration and oxidative stress,” is based on that by Sastre et al. In the original, the x-axis represents the lactate-to-pyruvate ratio in blood and the y-axis the GSSG-to-GSH ratio.
ROS are a major destructive factor of morphological structures of muscle fibers. (Pshennikova, 1986)
It has been suggested that ROS hyper-production in soft and connective tissues and bones may be the cause of degenerative changes, micronecrosis, and loss of elasticity that facilitate injuries. (Tabarchouk et al., 2014)
Adrenaline, the Hormone of Prey
Peroxidation of lipids (POL) intensifies during stress, regardless of the stress’ nature.(Baraboy, 1991) Emotional-pain stress causes activation of POL in the brain and thenexecutive organs (Meerson, 1981); POL concentration goes up two or three-fold. (Prilepko et al., 1983) High doses of catecholamines are accompanied by an increase of POL products in mitochondrial membranes by almost 90 percent. (Swaroop & Ramasarma, 1981)
“Adrenergic stimulation decreases [antioxidant] GSH synthesis.” (Estrella et al., 1988)
The adrenaline/noradrenaline hypothesis of fear and anger (Funkenstein, 1955) “is a good but not an exhaustive hypothesis to account for the characteristics of the respective autonomic responses.” (Potegal et al., 2010)
Adrenaline-to-noradrenaline ratios in different species. (von Euler, cited in Green, 1987; Rome & Bell, 1983)
Social animals, domestic and wild, have a high adrenaline-to-noradrenaline ratio. (Reed, 1958)
A creative “high” that increases physical and mental work capacity is accompanied by noradrenaline secretion. (Yakovlev, 1974)
Adrenaline and noradrenaline appear to be is associated with, respectively, uncertainty and certainty of outcome. (Kety, cited in McNaughton, 1989)
The Quick and the Dead
“Whereas a trained athlete can recover from a 100-meter sprint in 30 minutes or less, an alligator may require many hours of rest and extra oxygen consumption to clear the excess lactate from its blood and regenerate muscle glycogen after a burst of activity... Dinosaurs and other huge, now-extinct animals probably had to depend on lactic acid fermentation to supply energy for muscular activity, followed by very long recovery periods during which they were vulnerable to attack by smaller predators better able to use oxygen and better adapted to continuous, sustained muscular activity.” (Nelson & Cox, 2012)
Quote. (Lane, 2010)
Adaptation to muscular activity may be accompanied by adaptation to other stimuli: hypoxia, heat, cold, etc. (Rousin, 1984) Competition for oxygen unites these cross adaptations (Platonov et al., 2004) and many take place in the mitochondria (Yakovlev, 1974).
“For all the differences introduced by the specificity of the stimuli (cold, hypoxia, intense muscle work, etc.), the adaptation mechanism is characterized by pronounced generality (Meerson, 1973; Kaznacheev, 1980)…the same change takes place in cells of many physiological systems—a deficit of energy rich phosphate compounds and an increase in phosphorylation potential. This activates the cells’ genetic apparatus, intensifying synthesis of nucleic acids and proteins.” (Verkhoshansky, 1985)
“The metabolic role of mitochondria is so critical to cellular and organismal function that defects in mitochondrial function have very serious medical consequences. Mitochondria are central to neuronal and muscular function, and to the regulation of whole-body energy metabolism and body weight. Human neurodegenerative diseases, as well as cancer, diabetes, and obesity, are recognized as possible results of compromised mitochondrial function, and one theory of aging is based on a gradual loss of mitochondrial integrity. ATP production is not the only important mitochondrial function; this organelle also acts in thermogenesis, steroid synthesis, and apoptosis (programmed cell death).” (Nelson & Cox, 2012)
Mitochondria die and turn over. Mutations accumulate. “This creates an aging clock that progressively erodes our energetic capacity until there is insufficient energy flow for optimal tissue function, at which point symptoms ensue...As the severity of the energy defect increases, more systems become affected until death ensues.” (Wallace, 2011)
“The higher the mitochondrial content per gram of muscle, the lower the rate of respiration required per mitochondrion for any given workload.” (Hood, 2001) An increase in the number of mitochondria leads to a decrease in oxidation by free radicals in the muscles during intense exercise due to a decrease in production of ROS in the mitochondria. (Boveris & Chance, 1973; Davies et al., 1981; Jenkins et al., 1983)
“Numerous randomized studies have, in general, failed to demonstrate a benefit from antioxidant therapy and large meta-analysis studies su
ggests that in some cases, certain antioxidants may actually increase mortality…it is possible that the hint that antioxidants might increase cancer incidence may be a result of the ability of antioxidants to protect genetically damaged precancerous cells from undergoing apoptosis. Nonetheless, it is also possible that chronic low dose antioxidants inhibit the normal hormetic response and therefore block the induction of a broad array of cytoprotective measures the organism would normally undertake.” (Yun & Finkel, 2014)
“Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.” (Ristow et al., 2009)
“Antioxidant supplementation does not offer protection against exercise-induced lipid peroxidation and inflammation and may hinder the recovery of muscle damage.” (Teixeira et al., 2009)
“ROS-defenses are severely undermined in structurally compromised mitochondria…and that turns mitochondria into net producers of ROS…Intact mitochondria serve as a net sink rather than a net source of ROS.” (Andreyev et al., 2004)
PART II: THE FEROCITY OF LIFE
A Long and Winding Road
“Endurance traditionally has been associated with the necessity to fight fatigue and with increasing the athlete’s organism’s tolerance to unfavorable changes in the internal environment. It was thought that endurance is developed only when athletes reached the desired degrees of fatigue…Such views linked endurance to a fatalistically inevitable decrease in work capacity…and lead to a passive attitude towards endurance development…‘tolerate’ and put up with the unavoidable unpleasant sensations rather than actively search for training means that reduce fatigue, postpone it, and make it less severe.
“[Yet] the goal is not taking the athlete to exhaustion to accustom him to metabolic acidosis, as it is often understood in athletic practice, but just the opposite…to develop alactic power and to couple it with oxidative phosphorylation.
“…To be even more laconic, training must have an “anti-glycolytic” direction, that is lower glycolysis involvement to an absolute possible minimum.” (Verkhoshansky, 1988)
The Three Energy Systems
The approximate contribution of the three main energy systems to the total energy output in brief and all-out dynamic exercise graph is largely based on high-level athletes’ veloergometer data. (Volkov & Yaruzhny, 1984; Volkov et al., 2000)
The limitations of such a generalized graph become apparent once we consider the following data from what appears to be a highly homogenous group, the Finnish national team 100-meter sprinters. After a 40-meter sprint, less than five seconds, the slower ones (even though they were all sub-11 seconds) depleted nearly 43 percent of their CP and the faster ones around 63 percent. (Hirvonen et al., 1987)
This is just one of the many reasons why there are so many conflicting timelines of the energy systems’ contribution in the literature.
Nevertheless, to advance program design, generalize we must. And then, when necessary, individualize.
Since the rate of CP breakdown is modulated by the CP/Cr ratio, the ATP output of the creatine kinase reaction drops long before the CP is exhausted. (Sahlin, 2006)
The Emergency System
Quote. (Yakovlev, 1983)
The myokinase reaction takes place in muscles in conditions of pronounced muscular fatigue, when the rate of ATP resynthesis no longer balances out the rate of ATP hydrolysis and there is a significant increase in ADP concentration. The MK reaction is easily reversible. (Volkov et al., 2000)
The myokinase reaction is observed in all-out sprints longer than 10–15 seconds. (Spriet, 2006)
Intensity is Not the Effort, but the Output
Products of ATP hydrolysis induce synthesis of mitochondrial proteins on the genetic level. (Meerson, 1971)
AMPK is the “master switch” that triggers MT biogenesis in fast-twitch fibers. AMPK controls PGC-1α and mitochondrial enzyme gene expression in skeletal muscle. (Jäger et al., 2007) AMPK is a low cellular energy sensor that measures the AMP/ATP ratio, so on the cellular level, it is activated by a high AMP/ATP ratio. (Gowans & Hardie, 2014)
100 percent intensity represents MAP. (Selouyanov, 1991) “Maximum Anaerobic Power (MAP)…[is] the ability to effectively execute short-term (10–15 seconds) anaerobic work at the maximum level of power output.” (Verkhoshansky, 2011)
“If exercise…intensity falls low enough that glycolysis or the aerobic system can match energy consumption rates, then the cellular concentration of ATP will increase.” (Stone et al., 2007)
Muscular ATP balance disruption starts taking place at different intensities, depending on the athlete’s level. (Yakovlev, 1974) All athletes, from beginners to Masters of Sport, experience serious disruption of ATP balance in their muscles when running 100–400 meters in competition, but not at longer distances, with the exception of low-level athletes who experience it at 800 meters as well. (Krasnova et al., 1972)
Note the CP mechanism’s contribution at the above distances and 800 meters:
There is a linear relationship between the exercise intensity and the rate of CP depletion. (Volkov et al., 2000)
…And Then the Wheels Come Off
A single Wingate long sprint strongly activates AMPD (Bogdanis et al., 1995; Esbjörnsson-Liljedahl et al., 1985; Hargreaves et al., 1998); resting plasma ammonia concentration six minutes after a Wingate test reached 441 percent of the base level (Bogdanis et al.,1995). Thus, even though a single Wingate sprint increases the AMP/ATP ratio by as much as 21 times (Morales-Alamo et al., 2013), we consider the 30-second duration excessive and inefficient.
“Mammalian skeletal muscle has evolved to minimize the loss of ATP to IMP and IMP to inosine and hypoxanthine during exercise and recovery from exercise, as IMP resynthesis requires de novo synthesis of the adenine nucleotides, which takes some time. For example, other species (fish) will degrade all of the ATP stored in the muscle to IMP through the above reactions and much of the IMP to its degradation products in an extreme, life-threatening sprint situation. (Pearson et al., 1990) These animals then require six to twelve hours to regenerate the adenosine backbone in order to return to the resting concentration of ATP to normal.” (Hargreaves, 2006)
“[In silico] CFS simulations exhibit critically low levels of ATP, where an increased rate of cell death would be expected. To stabilize the energy supply at low ATP concentrations the total adenine nucleotide pool is reduced substantially causing a prolonged recovery time even without consideration of other factors, such as immunological dysregulations and oxidative stress. Repeated exercises worsen this situation considerably. Furthermore, CFS simulations exhibited an increased acidosis and lactate accumulation consistent with experimental observations.” (Lengert & Drossel, 2015)
There appears to be a strong correlation between blood lactate and ammonia in brief intense exercise. Goldman & Lowenstein (1977) concluded that the purine nucleotide cycle in skeletal muscles operates under the conditions “associated with an increased rate of glycolysis.” In both trained sprinters and long distance runners, there is a significant relationship between peak blood ammonia and lactate after supramaximal veloergometer exercise. (Itoh & Ohkuwa, 1990)
There was a sharp increase in adenine nucleotide pool degradation in untrained subjects in treadmill exercise when the BLa reached around 9mM. “The data further support the hypothesis that there is a critical intramuscular pH below which there is a stimulus to AN degradation during intense exercise, possibly as a result of a substantial reduction in the kinetics of adenosine diphosphate (ADP) rephosphorylation provided by phosphocreatine, resulting in an increase in [ADP].” (Sewell et al., 1994)
In elite 400-meter sprinters and hurdlers, blood lactate and ammonia displayed a strong correlation. (Gorostiaga et al., 2010) The researchers stressed that when the blood lactate levels do not exceed 8�
��12mM, the muscles’ energy status and maximal running velocity or muscle generating capacity are maintained—while higher levels decrease all of the above and delay functional recovery.
In all-out dynamic exercise muscle [La] barely rises above the resting levels for the first five seconds. Then lactate concentration approximately doubles from five to 10 seconds, from 10 seconds to 20, from 20 seconds to 30, and from 30 seconds to 60. (Volkov et al., 2000)
In trained athletes muscular activity produces significantly less deamination byproduct IMP and more ADP and AMP than in untrained people. (Yakovlev, 1971) Among the adaptations to exercise is reduced deamination of AMP and ADP. (Yakovlev, 1974) Overtraining lowers one’s resistance to deamination. (Yakovlev, 1974)
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