title: Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart.
abstract: S-Adenosylhomocysteine hydrolase of mammalian hearts from different species is exclusively a cytosolic enzyme. The apparent Km for the guinea-pig enzyme was 2.9 microM (synthesis) and 0.39 microM (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 to 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-adenosyl-homocysteine 17-fold to 64.3 nmol/g within 15 min. In the presence of 4-nitro-benzylthioinosine (5 microM), an inhibitor of adenosine transport, S-adenosylhomocysteine further increased to 150 nmol/g. L-Homocysteine thiolactone decreased the hypoxia-induced augmentation of adenosine, inosine and hypoxanthine in the tissue and the release of these purines into the coronary system by more than 50%. Our findings indicate that L-homocysteine can profoundly alter adenosine metabolism in the intact heart by conversion of adenosine into S-adenosylhomocysteine. Adenosine formed during hypoxia was most probably generated within the myocardial cell.
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D002415:Cats; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006710:Homocysteine / Q000494:pharmacology; D006867:Hydrolases / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D011817:Rabbits; D051381:Rats; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D013045:Species Specificity
chemical_list: D006710:Homocysteine; D012435:S-Adenosylhomocysteine; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine