ADO also has receptor-independent effects, because extracellular adenosine can cross the cell membrane and activate AMP-activated protein kinase (AMPK), adenosine kinase
, and S-adenosyl homocysteine hydrolase pathways .
It is rapidly transported back into cells and degraded into inosine or phosphorylated back to adenosine monophosphate (AMP) by adenosine deaminase and adenosine kinase
, respectively .
Adenosine can also be converted back to AMP by adenosine kinase, an enzyme that converts adenosine to AMP, or irreversibly converted to inosine by adenosine deaminase, an enzyme degrading adenosine to inosine .
Zhang, "Nitric oxide-stimulated increase in extracellular adenosine accumulation in rat forebrain neurons in culture is associated with ATP hydrolysis and inhibition of adenosine kinase activity," The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, vol.
Intracellularly, adenosine is metabolized by adenosine kinase
to AMP, whereas, extracellularly, it is degraded by adenosine deaminase to inosine [68-70].
Masino and her colleagues found that mice with normal levels of adenosine A1 receptor (ALP,) and a transgenic overexpression of adenosine kinase
, an intracellular enzyme that negatively influences extracellular levels of adenosine, had a "near complete" reduction in the number and duration of spontaneous seizures.
In this biosynthetic pathway, purine nucleoside phosphorylase (punA) that converts adenosine to adenine, adenosine kinase that converts adenosine to adenosine 5'-monophosphate (AMP), adenine phosphoribosyltransferase (APRT) that converts adenine to AMP, AMP deaminase that converts AMP to IMP, inosine monophosphate (IMP) dehydrogenase that converts IMP to XMP, guanosine monophosphate (GMP) synthase that converts XMP to GMP, and guanine deaminase that converts GMP to guanine were, respectively, determined (Figure 1).
One punA gene, one adenosine kinase gene, one APRT gene, two AMP deaminase genes, two IMP dehydrogenase genes, three GMP synthase genes, and two guanine deaminase genes were successfully cloned (Figure S3, Supporting Information), and the corresponding proteins expressed in E.
Adenosine kinase, adenylate kinase, and 5,-nucleotidase, which are involved in adenosine metabolic pathway and show the effects of phosphorylation and dephosphorylation, may also be involved in the biosynthetic pathway of 3'-deoxyadenosine .
There is recent evidence that blockade of adenosine kinase
, which results in increased endogenous levels of adenosine, downregulates the inflammatory response in experimental colitis .