Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart. 730 81

Relative to lymphoid cells and normal fibroblasts, mouse melanoma cells (B16) were moderately sensitive to adenosine, with 80% growth inhibition being observed at 50 micro M adenosine instead of at 5 micro M as was reported with lymphoid cells or 400 micro M as was reported for normal fibroblasts. These differences were not due to adenosine deaminase because lymphoid cells had two to four times more of this activity than did melanoma cells or normal fibroblasts. In melanoma cells, complete adenosine-induced growth inhibition was a gradual process which was observed only after one to two population doublings; after 4 days of treatment, complete recovery was gradual requiring 48 hr. N6,O2-Dibutyryladenosine-cyclic-3':5' phosphate and polyadenylic acid were ineffective as growth inhibitors, whereas guanosine exhibited potent growth-inhibiting properties. Homocysteine thiolactone enhanced the cytotoxicity of adenosine but not guanosine; adenosine relieved the cytotoxicity of guanosine. These observations indicated that the two purine nucleosides were exerting their growth-inhibiting effects by different mechanisms. Uridine did not relieve adenosine-induced cytostasis, but at 50 micro M adenosine enhanced the incorporation of [3H]uridine into RNA. This suggested that the uridine phosphate pools were depleted at low adenosine concentrations and that exogenous adenosine influences the availability of pyrimidines.
 ...
PMID:Characterization of adenosine-induced cytostasis in melanoma cells. 738 82