As part of our studies on polyamine biosynthesis in yeast, the metabolism of methylthioadenosine was studied in a mutant that lacks methylthioadenosine phosphorylase (meuI Delta). The nucleoside accumulates in this mutant and is mainly excreted into the culture medium. Intracellular accumulation of the nucleoside is enough to account for the inhibition of spermidine synthase and thus to indirectly regulate the polyamine content of the meu1 Delta cells. By comparing the results with this mutant with a meu1 Delta spe2 Delta mutant that cannot synthesize spermidine or spermine, we showed that > 98%, of methylthioadenosine is produced as a by product of polyamine synthesis (i.e., from decarboxylated S-adenosylmethionine). In contrast, in MEW SPE2(+) cells methylthioadenosine does not accumulate and is metabolized through the methionine salvage pathway. Using a metI5 Delta mutant we show that this pathway (i.e., involving polyamine biosynthesis and methylthioadenosine metabolism) is a significant factor in the metabolism of methionine, accounting for 15% of the added methionine. Published by Elsevier Inc.