ATP is the fuel that powers all cells-animal, plants, bacteria, fungi, etc. Such as a car without gas, humans and other creatures with an empty ATP “tank” do not go. In fact, they die. The energy derived from the breakdown of nutrients is ultimately conserved in the high energy phosphate bonds of ATP. When these bonds are broken, they provide accessible energy to cells, tissues, organs and organ systems. Cells constantly synthesize and metabolize ATP. ATP can be produced either aerobically through oxidative phosphorylation, with oxygen as the terminal electron acceptor and yielding carbon dioxide (CO2) and water as by-products, or anaerobically during glycolysis. While glycolysis can provide energy to cells, the supply is limited because the cellular environment becomes acidic, injuring the cell and inhibiting ATP production.
The vascular circulatory system delivers a continuous supply of energy that is derived from oxygen and nutrients. In the vasculature, a barrier of endothelial cells separates the cells being fed from the vessel lumen. To reach individual cells, oxygen and nutrients must pass through the endothelial lining into the interstitial space to deliver oxygen and nutrients. This oxygen supply can be cut off or reduced as a result of disease or trauma.
Supplying energy to cells would be preferably accomplished by direct administration of ATP; however, cells take up exogenous ATP poorly because they lack ATP receptors or channels. Furthermore, cell plasma membranes are hydrophobic, while ATP is hydrophilic, preventing the ATP from passing through. Introducing ATP into the blood stream is ineffective because ATP cannot cross the endothelial barrier, and ATP is prone to hydrolysis. Attempts to use liposomes to deliver ATP have been largely unsuccessful and inefficient (Arakawa et al. 1998, Puisieux et al. 1994). For example, Puisieux et al. constructed phosphatidyl choline, cholesterol and phosphatidyl serine lipid vesicles that encapsulated ATP, then incubated the vesicles with sperm cells, liver and brain tissue. Although some uptake was observed, controlled delivery matching metabolic demand for ATP was not achieved. When administered in the blood stream, liposomes are usually unable to breach the endothelial cell barrier; in addition, they usually do not have high rates of fusion with cellular membranes, a necessary event for the vesicle to deliver its ATP payload into the cells.
Animal cell plasma membranes contain four major phospholipids that represent greater than half of the total lipid: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and sphingomyelin. Phosphatidylcholine and sphingomyelin are found mostly in the outer leaflet, while phosphatidylethanolamine and phosphatidylserine are found principally in the inner leaflet. The predominance of the negatively-charged phosphatidylserine and phosphatidylinositol in the outer leaflet results in a net negative charge on the cells surface. Plasma membranes help maintain cellular integrity and are selectively permeable. While some molecules are able to diffuse through membranes, most, including ATP, require other means to enter, such as transport proteins or channels.