Comparison of the Effects of Adenosine, Inosine, and Their Combination as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction

Figure 2

Adenosine and inosine pathways in normal conditions. During “normoxia” adenosine is released in small amounts at a constant basal rate partly from hydrolysis of S-adenosyl homocystein (SAH) by SA-homocysteinase and mostly by dephosphorylation of AMP by 5′ecto-nucleotidases (5′EN) localized in the cytosol or membrane-bound outside the cells. From there, intracellular adenosine is rephosphorylated to AMP by adenosine kinase and a small amount is released from the cell. Indeed the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase which is much less active. Therefore, it is thought that 5′-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced. Inosine production depends on adenosine basal production. It is formed by the deamination of adenosine and is metabolized to ribose-1-phosphate and hypoxanthine by purine nucleoside phosphorylase and further to xanthine and uric acid by xanthine deshydrogenase. Consequently, plasma levels of free adenosine in normoxic conditions are extremely low (0.1-0.2 μmol/L) and those of inosine almost undetectable (0.01–0.1 μmol/L).