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

Biochemical Foundations of Human Vital Activity
Energy Metabolism in the Body
Regulation of ATP Metabolism

The rate of ATP synthesis depends on the rate of its utilization. In turn, the rate of ATP consumption depends on the speed of those processes in which ATP serves as an energy source (see Fig. 19). For instance, during muscular activity, ATP Cleavage in Muscles sharply increases. During the recovery period, ATP energy is also intensively utilized for the synthesis of Proteins and other plastic processes. The resulting ATP Hydrolysis products—ADP, AMP, and pyrophosphate—are rapidly incorporated into its resynthesis reactions in order to restore the initial physiological level of ATP.

One of the primary mechanisms regulating ATP METABOLISM in The Cell is the cellular energy charge, which is determined by The ratio of ATP, ADP, and AMP concentrations:

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Typically, the concentration of high-energy ATP in Cells significantly exceeds the combined concentration of AMP and ADP. The Energy balance of the system is 0.7–0.8. This state represents a physiological norm and is maintained at a constant level by metabolic processes. This means that the body's systems function with minimal Energy Expenditure, and the rate of ATP formation equals the rate of its utilization.

If the cell's energy charge decreases (The amount of ATP diminishes while ADP and AMP increase), the processes leading to ATP formation are accelerated, and those utilizing it are inhibited. Conversely, if the system's energy charge exceeds the normal level and reaches unity (high ATP, low ADP and AMP), ATP synthesis processes are suppressed, while its consumption processes are enhanced.

Creatine phosphate, a high-energy compound, participates in regulating the constant concentration of ATP within the cell. Mediated by the enzyme creatine phosphokinase (CPK), creatine phosphate readily transfers a phosphate group to ADP, helping to restore the physiological level of ATP in Tissues:

The creatine phosphokinase reaction is reversible. When the ATP content in cells rises, creatine phosphate is formed. Consequently, creatine phosphate acts as an energy reserve and an energy buffer that prevents an excessive increase in cellular ATP. A relatively constant level of ATP is maintained until the creatine phosphate reserves in tissues are significantly depleted.

The creatine phosphate content in specific types of Skeletal Muscle varies slightly, amounting to approximately 72–85 mmol·kg^-1 of dry Muscle tissue in slow-twitch muscles, and 82–89 mmol·kg^-1 in fast-twitch muscles. In contrast, the ATP content in these muscle types is roughly identical, at about 25 mmol·kg^-1 of dry muscle tissue.

V.A. Saks and other researchers substantiated the concept that creatine phosphate Functions in cells as an "energy-transport shuttle," meaning it transfers the energy stored in the high-energy bonds of ATP from Sites of production to sites of utilization (see Fig. 17). This is because free creatine molecules possess a high diffusion rate, which is almost an order of magnitude higher than that of ATP. Furthermore, cells contain various isoforms of the enzyme creatine phosphokinase (CPK) localized in different cellular compartments: on The inner mitochondrial membrane, the sarcoplasmic reticulum, myofibrils, the outer Plasma Membrane, and in the Cytoplasm.

Creatine phosphate is synthesized on the inner mitochondrial membranes through the transphosphorylation of free creatine and ATP, which is delivered from the mitochondrial matrix with the participation of a specific carrier protein—adenylate translocase (AT)—since ATP itself cannot independently migrate to the sites of energy utilization.

A portion of creatine phosphate is formed in the cytoplasm from ATP during Glycolysis. The resulting creatine phosphate easily diffuses into the cytoplasm and to other sites of its utilization.

With the participation of specific forms of creatine phosphokinase, ATP is generated from creatine phosphate and is immediately utilized either by Myosin ATPase, the Ca²⁺-ATPase of the sarcoplasmic reticulum, or the Na⁺-K⁺-ATPase of the Plasma Membranes. The liberated creatine returns to the Mitochondria, where ATP is synthesized via Oxidative Phosphorylation, and once again captures a high-energy phosphate from ATP. Due to this function of Creatine phosphate in Energy Metabolism, attempts are being made to use medicinal preparations of creatine phosphate or creatine to replenish or increase its level in the body.

Thus, the ratio of ATP, ADP, and AMP concentrations in cells regulates the rate of metabolic processes leading to ATP accumulation and utilization.

The mechanisms regulating ATP Synthesis and degradation are currently under intensive study because they form the energetic basis for controlling the rate of Muscle contraction and other ATP-dependent processes. It is also possible that in skeletal muscles, the rate of ATP synthesis during activity is regulated by Calcium Ions, the levels of which fluctuate during the contraction-relaxation cycle. Calcium influences oxidative phosphorylation by increasing the rate of ATP formation. Certain Hormones, such as adrenaline, also affect this process (see Chapter 8).

CONTROL QUESTIONS

1. Name the primary suppliers of energy in human body cells.

2. What substances are termed high-energy compounds? Provide Examples.

3. What is The Role of ATP in The transport of high-energy phosphate?

4. Write the structural scheme of the ATP molecule and its hydrolysis reaction.

5. Why does the ATP molecule function as an energy accumulator and carrier?

6. In which processes is ATP utilized?

7. Name the Main Pathways of ATP formation in the cell.

8. What are the concentrations of ATP and creatine phosphate in a muscle cell?

9. What is the role of creatine phosphate in ATP metabolism?

10. What is The Essence and significance of Biological Oxidation processes?

11. Name the Enzymes OF BIOLOGICAL oxidation and the Main Components of the Respiratory Chain.

12. What is meant by oxidative phosphorylation? What is its role in energy production?

13. How many ATP molecules are formed in the biological oxidation chain if NAD and FAD act as the primary hydrogen acceptors?

14. What is the role of the Krebs cycle in the biological oxidation of nutrients?

15. What is the energetic efficiency of the Krebs cycle?

16. What mechanisms regulating ATP metabolism in skeletal muscles do you know?