Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart

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Abstract
S-Adenosylhomocysteine hydrolase of mammalian hearts from different species [guinea-pig, cat, rat, rabbit, and dog] is exclusively a cytosolic enzyme. The apparent Km for the guinea-pig enzyme was 2.9 .mu.M (synthesis) and 0.39 .mu.M (hydrolysis). Perfusion of isolated guinea-pig hearts for 120 min with L-homocysteine thiolactone (0.23 mM) and adenosine (0.1 mM), in the presence of erythro-9-(2-hydroxynon-3-yl)adenine to inhibit adenosine deaminase, caused tissue contents of S-adenosylhomocysteine to increase from 3.5-3600 nmol/g. When endogenous adenosine production was accelerated by perfusion of hearts with hypoxic medium (30% O2), L-homocysteine thiolactone (0.23 mM) increased S-adenosylhomocysteine 17-fold to 64.3 nmol/g within 15 min. In the presence of 4-nitrobenzylthioinosine (5 .mu.M), an inhibitor of adenosine transport, S-adenosylhomocysteine further increased to 150 nmol/g. L-Homocysteine thiolactone decreased the hypoxiainduced augmentation of adenosine, inosine and hypoxanthine in the tissue and the release of these purines into the coronary system by more than 50%. L-Homocysteine can profoundly alter adenosine metabolism in thee intact heart by conversion of adenosine into S-adenosylhomocysteine. Adenosine formed during hypoxia was probably generated within the myocardial cell.