Effect of adenosine metabolites on methyltransferase reactions in isolated rat livers.
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.
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
D007042:Hypoxanthines; D014527:Uric Acid; D007288:Inosine; D012435:S-Adenosylhomocysteine; D008780:Methyltransferases; D000248:Adenosine Kinase; D000243:Adenosine Deaminase; D000241:Adenosine