Figure 3.

Purine metabolism and signaling in healthy and Huntington’s disease cardiomyocytes. In cardiomyocytes, ATP is heavily produced by mitochondria and transported to the cytosol through the phosphocreatine shuttle. In the cytosol, many enzymes (orange boxes) can convert ATP to AMP, ADO, IMP, inosine, and hypoxanthine. The later ones can be transported to the extracellular milieu by ENT. Extracellularly, ATP can also be converted to inosine through a similar cascade by extracellular-faced enzymes anchored to the cell membrane. CD73 is the only extracellular 5NT. Pathophysiology of Huntington’s disease exerts alterations in the activity of enzymes (marked in green +/−) or by genomic expression (marked in red +/−). P1—Adenosine receptor; P2X—ATP receptor channel; P2Y—ATP/UTP receptor; ATPases—adenosine-5′-triphosphatases; AK—adenylate kinase; eNTPD—ecto-nucleoside triphosphate diphosphohydrolase; AMPD—AMP deaminase; 5NT—5′ nucleotidase; CD73—ecto-5′ nucleotidase; eADA—ecto-adenosine deaminase; ADA—adenosine deaminase; PNP—purine nucleoside phosphorylase; ADSL—adenylosuccinate lyase; ADSS—adenylosuccinate synthetase; ENT—ecto nucleoside transporter. Created with BioRender.com (accessed on 5 May 20021).