Metabolic conversion of neplanocin A to S-neplanocylmethionine by mouse L 929 cells.

Treatment of mouse L cells with 1 microM Neplanocin A, results in the metabolic formation of the corresponding S-nucleosidylmethionine derivative. Identification of S-neplanocyl-L-methionine is based upon chromatographic analysis of the radiolabelled compound isolated from Neplanocin A-treated cells incubated with either [methyl-3H] or [carboxyl-14C]methionine and upon the results of in vivo studies using specific metabolic inhibitors. The intracellular level of this AdoMet analogue increases to approximately 500 pmoles/10(6) cells within 12 hours of Neplanocin A administration, after which it slowly decreases. The apparent metabolic utilization of this unique derivative is supported by our observation that it is capable of serving as a substrate for catechol-O-methyltransferase in vitro. These results provide evidence for a second mechanism by which Neplanocin A can affect cellular S-adenosylmethionine-dependent methylation reactions.