Regulation of cobalamin and folate metabolism by methionine in human bone marrow cultures.

In cobalamin deficiency folate metabolism is disturbed. In the liver this deranged metabolism can be overcome by methionine, however, methionine failed to overcome this abnormality in bone marrow cultures from cobalamin deficient patients. In cobalamin deficient E. coli mutant bacteria, methionine under different conditions could either inhibit or potentiate the growth of the organism. This study was therefore initiated to test the effect of methionine, under different conditions, on bone marrow cultures. The defective DNA synthesis in megaloblastic bone marrow due to cobalamin deficiency could be corrected by the in vitro addition of low 0.27 mumol (40 micrograms) but not high 6.7 mumol (1 mg) amounts of methionine. This was measured by the ability of deoxyuridine to suppress the 3H-thymidine incorporation into DNA. The effect of methionine in facilitating de novo DNA synthesis is probably due to the catalytic action of SAM which activates cobalamin dependent methyltransferase enzyme thus potentiating the effect of cobalamin. In contrast high concentrations of methionine may inhibit this enzyme.