The Importance of the Transmethylation Pathway for Adenosine Metabolism in the Heart

Summary

Measurements of transmethylation rate (approximately 750 pmol min⁻¹ g⁻¹) and total adenosine production rate (approximately 800 pmol min⁻¹ g⁻¹) in isolated, perfused guinea pig hearts have demonstrated that hydrolysis of S-adenosylhomocysteine is the primary source of intracellular adenosine during normoxia (95% O₂). Furthermore, adenosine kinase appears not to be substrate-saturated. When the rate of adenosine synthesis is increased 50-fold by hypoxic perfusion (30% O₂) there is little alteration in the rate of cellular transmethylation (approximately 1200 pmol min⁻¹ g⁻¹). Experiments using an adenosine analogue, tricyclic nucleoside (TCN), to selectively mark the intracellular 5′-AMP pool by conversion to TCN-monophosphate, demonstrated that hypoxia enhanced both adenosine and TCN release rates. These findings suggest that during hypoxia the primary source of adenosine is 5′-AMP and that the increased rate of 5′-AMP hydrolysis is due not only to an increased substrate concentration but also to deinhibition of 5′-nucleotidase.