title: Effect of adenosine metabolites on methyltransferase reactions in isolated rat livers.
abstract: Adenosine is rapidly metabolized by isolated rat livers. The major products found in the perfusate were inosine and uric acid while hypoxanthine could also be detected. S-Adenosylhomocysteine was also excreted when the liver was perfused with both adenosine and L-homocysteine. A considerable portion of the added adenosine was salvaged via the adenosine kinase reaction. The specific radioactivity of the resultant AMP reached 75-80% of the added [8-14C] adenosine within 90 min. When the liver was perfused with adenosine alone, hydrolysis of S-adenosylhomocysteine, via S-adenosylhomocysteine hydrolase, appeared to be blocked resulting in the accumulation of this compound. As the intracellular level of S-adenosylhomocysteine increased, the rates of various methyltransferase reactions were reduced, resulting in elevated levels of intracellular S-adenosylmethionine. When the liver was perfused with normal plasma levels of methionine the S-adenosylmethionine: S-adenosylhomocysteine ratio was 5.3 and the half-life of the methyl groups was 32 min. Upon further addition of adenosine the S-adenosylmethionine: S-adenosylhomocysteine ratio shifted to 1.7 and the half-life of the methyl groups to 103 min. In the presence of adenosine and L-homocysteine such inordinate amounts of S-adenosylhomocysteine accumulated in the cell that methylation reactions were completely inhibited. Although adenine has been found to be a product of the S-adenosylhomocysteine hydrolase only trace quantities of this compound were detectable in the tissue after perfusing the liver with high concentrations of adenosine for 90 min.
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000818:Animals; D007042:Hypoxanthines / Q000494:pharmacology; D066298:In Vitro Techniques; D007288:Inosine / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology
chemical_list: D007042:Hypoxanthines; D014527:Uric Acid; D007288:Inosine; D012435:S-Adenosylhomocysteine; D008780:Methyltransferases; D000248:Adenosine Kinase; D000243:Adenosine Deaminase; D000241:Adenosine