1.1 ATP: The energy currency in the cell
Adenosine Triphosphate (ATP) is a high-energy phosphate compound and the special carrier molecule of free energy in the body. It is formed from a molecule of adenine and ribose linked to three phosphates. The cleavage of ATP’s outermost phosphate bond through a hydrolysis reaction catalyzed by the enzyme, ATPase, results in the release of an inorganic phosphate ion (Pi) and 7.3 kCal of free energy per mole of ATP (equation 1). Infrequently, additional energy releases when another phosphate splits from ADP to result in AMP, with a single phosphate group.
Equation 1: Hydrolysis of ATP
The potential energy within the bonds of macronutrients (carbohydrates, lipids and proteins) is transferred into the energy stored in anhydride phosphate bonds of ATP through a series of stepwise redox reactions. Subsequently, energy from ATP hydrolysis may be transferred to other compounds to raise them to a higher activation level or it may be used to power mechanical, chemical and transport work. In exercise for example, ATP is required for muscular work as well as for maintaining ion gradients across the muscle and nerve cell membranes.
1.2 ATP as a source of stored energy within the muscle cell
Since ATP is a relatively heavy molecule, cells contain only a small quantity of stored ATP. Intramuscular ATP reserves are utilized for very short bursts of activity such as picking up a glass, swinging a golf club or performing a push-up.
The quick release of energy from ATP occurs rapidly from anaerobic hydrolysis of the ATP molecule to release energy (as shown in the equation 1).
These small increases in energy requirement immediately disrupt the balance between ATP and ADP and Pi, which stimulate several systems to increase energy transfer from stored energy-containing compounds within the cell (phosphocreatine and other macronutrients) to resynthesize ATP and restore balance.
1.3 Resynthesis of ATP from phosphocreatine
In scenarios where activity is sustained for a few seconds, ATP is rapidly resynthesized in muscle cells, primary from the phosphocreatine pathway.
Phosphocreatine (PCr) is a rapid and high-energy reservoir within the cell. A large amount of free energy is released when the bond between phosphocreatine and the phosphate molecule is cleaved by creatine kinase, generating -43.3 kJ/mol of free energy which can be stored by ATP (see equation 2). Due to its high energy storage potential, the intracellular concentration of PCr is approximately four to six times more than that of ATP.
Equation 2: The energy liberated from the hydrolysis of PCr rebonds ADP and Pi to form ATP. Creatine kinase is required for this reaction to occur.
The hydrolysis reaction of PCr reaches a maximum energy yield in about 10 seconds (very fast). However, even at its maximal effort, the enzyme creatine kinase, which is needed to catalyze the reaction for PCr breakdown, cannot supply long-term energy demands. Therefore the less-rapid catabolism of glycogen (stored form of glucose in the cell) and fat as energy sources are needed to meet further energy demands.
A second intracellular reaction can also release energy during periods of high demand. The adenylate kinase reaction represents another enzyme-mediated reaction for immediate ATP production by joining two molecules of ADP to form one molecule of ATP and AMP as shown in Equation 3. This reaction is less common in muscle, unless other sources of energy are lacking.
Equation 3: Adenylate Kinase Reaction
1.4. Resynthesis of ATP through phosphorylation/oxidation of macronutrients: carbohydrates, fats and proteins.
The maintenance of a limited intramuscular supply of ATP and the production of AMP, Pi and ADP mediated by phosphocreatine and adenylate kinase as mentioned above, rapidly stimulates the breakdown of macronutrients to resynthesize ATP at a rate equivalent to ATP’s rate of use and intensity of physical activity. While ATP hydrolysis occurs anaerobically enabling rapid energy transfer during strenuous short-lived physical activity; the resynthesis of ATP can be aerobic or anaerobic in the case of glucose metabolism or exclusively aerobic for lipid and protein metabolism.
Most of the energy for ATP generation derives from the aerobic phosphorylation/oxidation pathway, that is, the oxidation of carbohydrate, lipid and protein macronutrients as oxygen is reduced. Figure 1 depicts the oxidative pathways of carbohydrate, fat and protein macronutrients in ATP generation.
Figure 1. The citric acid cycle as the common oxidative pathway in ATP generation from carbohydrate, lipid and protein macronutrients. (For a more detailed version, consult McArdle, Katch & Katch Fig 6.19).
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