Re: What affect does direct ATP injection have?

Hello Nicodemus,

ATP does not freely diffuse across plasma membranes (PM) due to the fact that ATP is a highly charged polar molecule, which is a substantial barrier to crossing the hydrophobic portion of the PM. In general, small, polar molecules such as amino acids and nucleotides (including adenosine) are not freely permeable to the PM. Further complicating the specific case you describe is the fact that ATP has a total net charge of -4. The electric potential across the PM is ~70 mV, with the inside of the cell being more negative relative to the outside, meaning that there would be no passive diffusion up the electrical gradient across the PM. Thus, using 3-bromopyruvate in your example to deplete ATP followed by administration of ATP via an injection would not rescue the cells. One complication of injection is that extracellular ATP is that ATP is converted to adenosine in less than a second. ATP is readily hydrolyzed to ADP and AMP by membrane-bound CD39 (aka EctoATP diphosphohydrolase). AMP is further hydrolyzed by the intracellular enzymes 5-nucleotidase and adenosylhomocysteine hydrolase to adenosine. Adenosine itself has a half life of ~ 1 sec in the blood, as it is taken up by erythrocytes (red blood cells) and is itself a substrate for adenosine deaminase, which converts adenosine into inosine. Because ATP is rapidly catabolized, direct ATP injection would therefore have to occur close to the specific site of action in the body, and its effects would depend heavily upon the target tissue. But, to answer the specific question of what would happen if ATP were injected directly into a vein, the answer is probably not much.

Sincerely,

Anthony

References:

Lodish et al, Molecular Biology of the Cell, 3rd edition, Scientific American Books, 1995.

Voet & Voet, Biochemistry, 2nd edition, John Wiley & Sons, 1995.

http://www.pharmacorama.com/en/Sections/Adenosine.php