S-adenosylmethionine metabolism in HL-60 cells: effect of cell cycle and differentiation

The effect of the cell cycle and differentiation on S-adenosylmethionine (SAM) metabolism in HL-60 cells has been investigated. Synthesis and pool sizes of SAM and S-adenosylhomocysteine (SAH) were cell-cycle-independent (SAM, 315 microM; SAH, 4.6 microM). The SAM-synthase (ATP: L-methionine S-adenosyltransferase) of HL-60 cells has a Km for methionine of 12.8 +/- 2.0 microM and thus appears to be of the intermediate Km type found in other malignant tissues. The enzyme does not show cell-cycle regulation. Treatment of cells with DMSO resulted in a rapid and marked decrease of SAM and SAH levels without affecting pool turnover or the SAM/SAH ratio. A decrease in SAM concentration could also be observed in a variant cell line resistant to differentiation with DMSO. DMSO inhibited SAM-synthase in cell-free extracts. This inhibition was noncompetitive with respect to L-methionine. Inhibition of SAM-synthase by cycloleucine lowered SAM levels in intact cells, but resulted in differentiation of only a minor percentage of cells. These data indicate that changes in SAM and SAH levels in HL-60 cells seem to be a consequence rather than a cause of differentiation.