Effect of adenosine metabolites on methyltransferase reactions in isolated rat livers

Biochim Biophys Acta. 1981 Dec 4;678(2):275-82. doi: 10.1016/0304-4165(81)90217-8.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / metabolism*
  • Adenosine / pharmacology
  • Adenosine Deaminase / metabolism
  • Adenosine Kinase / metabolism
  • Animals
  • Hypoxanthines / pharmacology
  • In Vitro Techniques
  • Inosine / pharmacology
  • Kinetics
  • Liver / enzymology*
  • Male
  • Methyltransferases / metabolism*
  • Perfusion
  • Rats
  • S-Adenosylhomocysteine / pharmacology
  • Uric Acid / pharmacology

Substances

  • Hypoxanthines
  • Uric Acid
  • Inosine
  • S-Adenosylhomocysteine
  • Methyltransferases
  • Adenosine Kinase
  • Adenosine Deaminase
  • Adenosine