The Role of Adenosine-5’-triphosphate (ATP) in Cellular Function
An average human being is composed of between 70-100 trillion cells. Each of the cells have specific functions in the human body and require a constant supply of energy, or more precisely adenosine-5’-triphosphate (ATP) in order to survive. ATP has been coined the “universal energy currency of life” and for good reason . The role of ATP, as well as its degradation products (ADP, AMP, Adenosine, Inosine, Hypoxanthine, Xanthine, and Uric Acid) in both normal and abnormal cell function are enormous [2-7]. ATP is involved with creating proteins, carbohydrates, lipids, and nucleic acids, as well as an important role in cell signaling, and cell membrane potential. For these reasons, it is easy to understand why ATP is the universal energy currency of life.
Two major pathways are involved in cell ATP production: Glycolysis, which is the cell’s pathway to make ATP in the absence of oxygen, and oxidative phosphorylation, which uses the oxygen we breathe to create ATP. During periods of low oxygen (hypoxia) or decreased blood flow (ischemia), oxidative phosphorylation production of ATP significantly decreases, and the cells begin to produce lactic acid, which decreases the pH inside of the cell . Decreased cellular ATP triggers cells to increase glucose uptake in a futile attempt to increase glycolysis derived ATP, but since oxygen is decreased, the result is more lactic acid . The lower ATP and decreased intracellular pH results in a myriad of cell issues, the most notable being decreased cell membrane potential . The change in membrane potential results in opening of voltage-gated calcium channels , and entry of calcium inside of the cell. Increased intracellular calcium leads to activation of pathways that lead to apoptosis also known as programmed cell death .
While temporary hypoxia or ischemia can result in cell survival, prolonged hypoxia or ischemia can lead to cell death. However, even if oxygen and ATP are restored to “normal” levels, the survival of the cell is not guaranteed. The increase in oxygen results in increased levels of oxygen radicals that can lead to cell death (a process known as reperfusion injury). This affect can be seen when a limb or finger has been severed and reattached but was either without blood flow for too long a period or was not adequately stored (i.e. on ice) and begins to show the clinical hallmark signs of necrosis (cell death). Another excellent example of the role of ATP in ischemia is during hemorrhagic shock, or bleeding to death. As the blood supply of the body is lost during severe bleeding, the body’s blood vessels in the periphery of the body (e.g., legs, arms) constrict to help elevate central hemodynamic pressure to the heart, lungs and brain . The result is that the ischemic tissue, especially the intestines, has decreased intracellular ATP levels, this causes the releases of substances from the ischemic tissue . If resuscitation occurs and blood flow is restored to the ischemic tissue, the reperfusion injury results in increased leakage of fluid into other organs, which can lead to multi-system organ failure, and death. Studies have suggested that the use of ATP during progressive lethal shock can increase survival times in animals [15-17].
ATP has another important role in the body that is unrelated to the use of its high energy phosphate bonds. ATP is a potent cell signal that binds to purinergic receptors that result in various cell responses ranging from increased intracellular calcium, changes in membrane potential, mitochondrial dysfunction, and increased expression of growth factors, cytokines, and chemokines to name a few . The result of these events can be as diverse as increased cell proliferation to increased cell death. Many have suggested that since the cells of our body do not normally encounter increased extracellular ATP (any ATP leakage from the cell or ATP release by a few disrupted cells is quickly destroyed by ectonucleotidases-enzymes that breakdown ATP), that the concentration of extracellular ATP acts a measure of the extent of tissue damage . That is the more tissue damage the more ATP that is released by the damaged cells, resulting in events that help heal the damaged tissue. Tissue that borders the sight of damage would have the highest concentration of ATP, resulting in cell death and remodeling of the damaged area. Cells more distant to the tissue damage, and thus less extracellular ATP, would increase cell proliferation and cell signaling that results in tissue remodeling.
IN SUMMARY; LISTED BELOW ARE KEY ROLES OF ATP IN CELLULAR FUNCTION:
- Protein Synthesis
- Lipid Synthesis
- Carbohydrate Synthesis
- Nucleotide Synthesis
- Membrane Potential
- Ion Channel Function
- Intracellular Signaling
- Extracellular Signaling
- Protein Signaling
Gross Physiological Function*
- Muscle Contration (skeletal;, smooth, heart)
- Prevent Ischemia Reprofusion Injury
- Kidney Function
- Nerve Transmission
- Wound Repair
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