FIGURE 2.

MTX impact on adenosine secretion. MTX is polyglutamylated (MTXglu) after active transport of MXT into intracellular space. MTXglu inhibits AMP/adenosine deaminase (AMPDA/ADA respectively) and thus IMP/inosine production through accumulation of aminoimidazole carboxamidoribonucleotide (AICAR) and aminoimidazole carboxamidoribonucleoside (AICAside), the intermediate metabolites of purine biosynthesis. This results in increased cellular release of adenine nucleotides which are quickly converted into adenosine in the extracellular space. Adenosine triphosphate – ATP; adenosine diphosphate – ADP; adenosine monophosphate – AMP; adenylate deaminase – AMPDA; dihydrofolate polyglutamate - DHFglu; formyl AICAR - FAICAR; Inosine monophosphate – IMP; inosine triphosphate – ITP; inosine triphosphate pyrophosphatase – ITPA; reverse folate carrier 1 – RFC1; adenosine kinase – AK; nucleoside triphosphate phosphohydrolase – NTPDase; ecto-5’ nucleotidase – Ecto-5’ NT.