1988 Volume 3 Issue 3 Pages 287-300
The biotransformation of S-adenosyl-L-methionine sulfate tosylate (FO-1561) was studied in rats after intravenous administration of 14C-labeled FO-1561 at a dose of 10 mg (as S-adenosyl-L-methionine)/kg.
1. After intravenous administration of [Ade-8-14C] FO-1561 to rats, allantoin, uric acid and unchanged S-adenosyl-L-methionine were identified in the urine as major metabolites. Homoserine, cystathionine and methionine were identified after intravenous administration of [Met-2-14C] FO-1561. After intravenous administration of [CH3-14C] FO-1561, the radioactive methyl group was incorporated into creatine and creatinine in the skeletal muscle, and into phosphatidylcholine and N-methylated phospholipids of the brain, liver and kidney. These results suggest that exogenous S-adenosyl-L-methionine is metabolized through purine metabolic pathway and transmethylation.
2. After intravenous administration of [Met-2-14C] FO-1561 to rats, there was high concentration of S-adenosyl-L-methionine in the plasma, but it almost disappeared within 6 hr. On the other hand, there were low concentrations of S-adenosyl-L-methionine in the brain and liver, and then these levels decreased gradually. There was extremely high concentration of S-adenosyl-L-methionine in the kidney, and its maximum concentration was reached at 1 hr, and then it disappeared within 120 hr. In addition, there was high concentration of S-adenosylhomocysteine in the kidney.
3. After administration, the S (−) ratio of S-adenosyl-L-methionine in the plasma decreased with time, and markedly decreased in the liver and kidney. Therefore it was suggested that S (−) form of S-adenosyl-L-methionine could be utilized selectively in the tissue.
4. On the basis of these results, the metabolic pathways of FO-1561 in rats were discussed.
