METABOLISM OF 5′-METHYLTHIOADENOSINE IN METHIONINE DEPENDENT AND INDEPENDENT CELLS: 33

Abstract

Methionine (Met) dependency was investigated in a Met-dependent (CCL 39) and in a Met-independent (Raji) cell line. Met dependency was similarly observed with two Met precursors, L-homocysteine and 5'-deoxy-5'-methylthioadenosine (MTA), suggesting that this phenomenon represents, in fact, the inability of a cell to grow on a metabolic precursor of Met. The study of MTA metabolism in CCL 39 and Raji cells indicates that Met dependency is not due to the inability to synthetize Met from MTA, nor to incorporate newly synthetized Met into proteins, nor into S-adenosylmethionine (SAM). However, there are differences in SAM metabolism and disposition between CCL 39 and Raji cells. The synthesis of SAM from labelled MTA is higher in CCL 39 than in Raji cells, but SAM is much more excreted by CCL 39 than by Raji cells, with ratios of extracellular to intracellular SAM of 20.3 and 5.1, respectively. However, when the cells are incubated with labelled Met, the synthesis of SAM is similar in both types of cells, and the ratios of extracellular to intracellular SAM are much lower than in the previous case (0.8 and 1.0 for CCL 39 and Raji cells, respectively). These results, and the fact that exogenous unlabelled Met moderately affects the incorporation of labelled MTA into intracellular SAM by CCL 39 cells, and profoundly depresses it in Raji cells, support the hypothesis of a metabolic compartmentation of exogenous and endogenous Met in Met-dependent cells.