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Xylosyl-MTA, an analog of MTA, is a secondary metabolite of the marine mollusc Doris verrucosa. Biochemical studies conducted to evaluate the effect of this compound on the enzymes involved in MTA metabolism have demonstrated that it does not interfere with MTA catabolism and with its regulatory effects on polyamine biosynthesis.

5?-Deoxy-5?-methylthioadenosine (MTA) is a naturally occurring sulfur nucleoside, ubiquitously distributed in nature endowed with antiproliferative activity (1-4). It derives from S-adenosylmethionine (AdoMet) metabolism through several metabolic pathways (1-4). In mammalian tissues the spermidine synthase and spermine synthase reactions represent the quantitatively most important routes for MTA formation (1-4). In spite of the occurrence of multiple biosynthetic pathways, the intracellular concentration of MTA is remarkably low when compared with that of spermidine, spermine and AdoMet (5-8). The thioether indeed does not accumulate intracellular ly because of its rapid cleavage by MTA phosphorylase into adenine and 5-methylthio-ribose-1-phosphate (9).

The biosynthesis of 9-[5′-deoxy-5′-(methylthio)-beta-D-xylofuranosyl]adenine (xylosyl-MTA), a naturally occurring analogue of 5′-deoxy-5′-methylthioadenosine (MTA) recently characterized, was studied in the nudibranch mollusc Doris verrucosa. Experiments performed in vivo with putative labelled precursors such as [8-14C]adenine, [Me-14C]methionine and [Me-14C]MTA indicate that xylosyl-MTA originates from MTA. Experiments with MTA double-labelled at critical positions are consistent with a 3′-isomerization of the nucleoside through the formation of a 3′-oxo intermediate. In addition, experiments with the newly synthesized [3′-3H]xylosyl-MTA are indicative for a very low turnover rate of this molecule, which therefore accumulates in the mollusc.