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Some mechanisms of adenosine formation and metabolism

ADO ADO

Na-purine co- Equilibrative ADO
transporter transporter

ADO

Ino AMP

Hcy AMP IMP Ecto-
nucleotidases

AdoHcy Me cAMP ATP
SAM

cAMP

FIGURE 1. Schematic representation of the mechanisms by which adenosine levels are

regulated.

In contrast, the clearance of extracellular adenosine is better
understood. It mostly occurs through the action of the non-concentrative
adenosine transporters, and the effectiveness of the uptake system is
guaranteed by the efficient intracellular metabolisation of adenosine.
Indeed, adenosine can either be converted into inosine through adenosine
deaminase or be phosphorylated into AMP via adenosine kinase. The
comparison of the kinetic parameters of each of the enzymes lead to the
proposal that adenosine kinase was the initial pathway to salvage
intracellular adenosine, with adenosine deaminase only coming to play
when large amounts of adenosine have to be cleared. This is confirmed by
the general greater effectiveness of adenosine kinase inhibitors to increase
the extracellular levels of adenosine under physiological situations and
the increased effectiveness of adenosine deaminase inhibitors to increase
the extracellular levels of adenosine with increased neurotoxic insults.

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