Biochemical Foundations of Human Vital Activity - Volkov, N.I., Nesen, E.N. 2000

Biochemistry of Sports
Bioenergetics of Muscular Activity
Glycolytic Mechanism of ATP Resynthesis

As soon as the Creatine Phosphokinase Mechanism fails to provide the required rate of ATP resynthesis in Muscles during anaerobic muscular activity, the anaerobic glycolytic Mechanism of ATP resynthesis is recruited into energy supply. Glycolysis primarily utilizes intramuscular Glycogen stores as well as Blood-borne glucose. These are gradually broken down into lactic acid through a multi-enzyme pathway (Fig. 124). The enzymatic process of glycolysis is discussed in detail in Chapter 9.

Most glycolytic Enzymes are localized in the sarcoplasm of Muscle fibers. The enzymes phosphorylase and hexokinase, which drive the initial reactions of glycolysis, are readily activated by increasing concentrations of ADP and inorganic phosphate in the sarcoplasm. Furthermore, The formation of active phosphorylase is stimulated by catecholamines and Ca²⁺ ions, the levels of which rise During Muscle contraction. All of this ensures that glycolysis rapidly contributes to ATP resynthesis from the very first seconds of activity, as evidenced by the increasing concentration of lactic acid in muscles (see Fig. 123).

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Fig. 124 Diagram of the glycolytic mechanism of ATP resynthesis in skeletal muscles: 1 — Myosin ATPase; 2 — PCr (sarcoplasm); 3 — adenylate kinase (myokinase); 4 — hexokinase; 5a — phosphorylase a (active form); 5b — phosphorylase b (inactive form); 6 — Phosphofructokinase; 7 — G3P dehydrogenase; 8 — phosphoglycerate kinase; 9 — Pyruvate kinase; 10 — Lactate dehydrogenase

Hydrolysis is also facilitated by a decrease in muscle creatine phosphate concentration and the accumulation of AMP generated during the myokinase reaction of ATP resynthesis.

In summary, the processes of glycolysis and Glycogenolysis can be represented by the following equations:

The energy yield of glycolysis when starting from glucose is 2 moles of ATP per 1 mole of carbohydrate broken down, whereas for glycogenolysis, starting from muscle glycogen, it is 3 moles of ATP per 1 mole of cleaved glucose equivalent.

The peak power of glycolysis can reach 3.1 kJ ⋅ kg^-1 ⋅ min^-1 in highly trained athletes, compared to 2.5 kJ ⋅ kg^-1 ⋅ min^-1 in untrained individuals. While somewhat lower than the power of the creatine phosphokinase reaction, this is 2–3 times higher than the power of the aerobic process. This mechanism reaches its maximum output within 20–30 seconds of commencing work, meaning its activation rate is considerably slower than that of the creatine phosphokinase system. By the end of the 1st minute of work, glycolysis becomes the primary mechanism of ATP resynthesis. However, prolonged activity leads to a decline in The activity of key glycolytic enzymes due to accumulating lactic acid or falling intracellular pH, which ultimately reduces The rate of ATP resynthesis via this pathway.

The metabolic capacity of glycolysis, determined by intramuscular carbohydrate stores and dependent on the buffering capacity of systems stabilizing intracellular pH, sustains anaerobic exercise lasting from 30 seconds to 2–6 minutes.

The total energy produced via The Glycolytic Pathway in untrained individuals does not exceed 840 kJ ⋅ kg^-1, which corresponds to a blood lactic acid concentration of approximately 13 mmol ⋅ l^-1, representing their physiological threshold. In athletes who incorporate anaerobic glycolytic training into their regimens, the lactate capacity reaches 1760–2090 kJ ⋅ kg^-1, corresponding to blood lactate levels within 25–30 mmol ⋅ l^-1. Nevertheless, in endurance-trained athletes, post-exercise blood lactic acid concentration generally does not exceed 10–13 mmol ⋅ l^-1, depending on the proportion of fast-twitch fibers in their skeletal muscles.

The glycolytic mechanism of ATP resynthesis has a relatively low efficiency: during the anaerobic breakdown of 1 mole of glucose, only 240 kJ of energy is released out of the 2880 kJ total content. The majority of the energy remains trapped in the resulting lactic acid molecules and can only be liberated through aerobic oxidation. Of the total energy released during glycolysis, roughly 80 to 125 kJ is converted into usable high-energy phosphate bonds of ATP, while the remainder is dissipated as heat. Consequently, the metabolic efficiency of glycolysis is estimated at an efficiency ratio of 0.35–0.52. This means that roughly half of all liberated energy is converted into heat and cannot be harnessed for work. As a result, glycolytic activity accelerates heat production in working muscles, elevating their Temperature to 41–42 °C.

Glycolysis plays a vital role during intense muscular activity under conditions of inadequate tissue oxygen supply. It serves as the primary energy-generating pathway in submaximal power exercises, the maximum duration of which ranges from 30 s to 2.5 min (such as middle-distance running, 100-m and 200-m swimming, track cycling, etc.). Glycolysis fuels sustained accelerations throughout the exercise and at the finish line. This glycolytic energy-producing mechanism forms the biochemical basis for specialized speed endurance in the body.

The glycolytic pathway of ATP resynthesis is accompanied by the accumulation of lactic acid in the muscles, the concentration of which is directly dependent on the power and total duration of the exercise (Fig. 125).

In an aqueous environment, lactic acid dissociates into ions, altering the hydrogen ion concentration and the pH of the intracellular environment:

Fig. 125 Formation of lactic acid during glycolysis as a function of exercise duration

A moderate shift in pH toward the acidic side activates the respiratory cycle enzymes in Cell/35.html">Mitochondria and enhances aerobic energy production. A significant change in muscle pH from 7.1 at rest to 6.5 upon exhaustion inhibits the enzymes that regulate the rate of glycolysis and muscle contraction. At an intramuscular pH of 6.4, glycogen breakdown ceases, leading to a sharp drop in ATP levels and the onset of fatigue.

An increase in The amount of lactic acid in the muscle sarcoplasm is accompanied by A change in osmotic pressure. As a result, Water from the intercellular environment enters the muscle fibers, causing them to swell, which can compress nerve endings and cause muscle pain.

Lactic acid can diffuse across cell membranes down a concentration gradient, passing from working muscles into the blood. Typically, the maximum accumulation of lactic acid in the blood is observed 5–7 min post-exercise. Lactic acid interacts with the bicarbonate blood buffer system, leading to the formation of a "non-metabolic" excess of CO₂:

An increase in hydrogen ion concentration and a rise in blood CO₂ tension stimulate the respiratory center; therefore, when lactic acid enters the bloodstream, pulmonary ventilation and oxygen delivery to working muscles increase dramatically. A significant accumulation of lactic acid, the appearance of excess CO₂, a change in pH, and pulmonary hyperventilation—reflecting intensified glycolysis in the muscles—are detected when exercise intensity exceeds 50% of the maximum aerobic power (Fig. 126). This load level is referred to as the anaerobic threshold (AnT) or lactate threshold (LT). The earlier it is reached, the faster glycolysis is triggered, accompanied by the accumulation of lactic acid and the subsequent development of fatigue in working muscles.

The AnT value is an important indicator of the METABOLISM/25.html">Efficiency of Energy-generating processes in muscles, the intensity of training loads, and the growth of fitness levels, and it is widely used in the Biochemical Monitoring of an athlete's functional state (see Chapter 24). The anaerobic threshold can be determined using various indicators shown in Fig. 126. However, the most well-founded approach is the method of plotting individual curves of blood lactate concentration (La) versus physical work rate, expressed either in watts (W) or as a percentage of $\dot{V}\text{O}_2\text{max}$. A sharp inflection in the curve indicates the transition of the muscles to an anaerobic working mode, after which the lactic acid concentration will increase with load intensity due to enhanced glycolysis (Fig. 127, a). In many athletes, the AnT corresponds to a lactic acid level of 2–4 mmol ⋅ L^-1. As endurance fitness improves, the lactate threshold increases, meaning it occurs at a higher work intensity (see Fig. 127, b).

Fig. 126. Determination of the anaerobic threshold (AnT) based on the curves of blood lactate concentration, blood pH, pulmonary ventilation level, and "excess CO₂ output" as a function of exercise intensity

Recently, a simpler method has been used to assess metabolic adaptation processes by measuring blood lactic acid concentration solely after a single standard specific exercise test at a fixed speed. As the body's level of fitness increases through various training stages, the concentration of blood lactic acid following such a load decreases (Fig. 128).

Fig. 127. Determination of the anaerobic threshold from the inflection point of the lactate accumulation curve during incremental exercise (a), and Changes in the anaerobic threshold following endurance training (b)

Fig. 128. Changes in blood lactate concentration after a 200 m swim at a set speed in swimmers over the course of multi-month training