Methionine synthesis from 5'-methylthioadenosine by tumour cells

Incubation of cytosolic fractions of some tumour and normal cell lines with 5'-methylthioadenosine (5'-MTA) resulted in the formation of methionine. Methionine formation only occurred in those cell lines possessing 5'-MTA phosphorylase. The kinetics of product formation indicated that 5'-MTA was first rapidly converted into 5-methylthioribose-1-phosphate, followed by its slower conversion into methionine. Methionine synthesis from 5'-MTA was increased in cells previously incubated in methionine-depleted medium supplemented with 0.1 mM L-homocysteine for 24 hr. For most cell lines methionine synthesis from 5'-MTA was linear for only a short time period, and was followed by a first order decrease in the rate of methionine synthesis. Methionine synthesized from 5'-MTA was extensively incorporated into cellular macromolecules suggesting that 5'-MTA may substitute for methionine as a one-carbon source. This was confirmed by growth experiments which showed that low concentrations of 5'-MTA could partially substitute for methionine for some, but not all, cell lines. Higher concentrations of 5'-MTA were growth inhibitory. It may be possible to use 5'-MTA to selectively 'rescue' cells from methionine deprivation produced by the enzyme L-methioninase.