SYNTHESIS OF COBALAMIN COENZYMES BY HUMAN LYMPHOCYTES INVITRO AND EFFECT OF FOLATES AND METABOLIC-INHIBITORS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 48  (4) , 609-619
Abstract
The uptake of 57Co-cyanocobalamin (CN-Cbl) and its conversion to 5-deoxyadenosylcobalamin (Ado-Cbl), methylcobalamin (Me-Cbl) and hydroxocobalamin (OH-Cbl) was studied in phytohemagglutinin (PHA)-transformed lymphocytes from normal subjects and patients with pernicious anemia. Uptake and conversion were much greater by PHA-stimulated lymphocytes than by mature non-transformed lymphocytes. In normal cells, uptake of 57Co-CN-Cbl and synthesis of the cobalamin coenzymes were approximately linear between 3 and 48 h incubation. Ado-Cbl was the major cobalamin formed, and after 72 h the cells contained about twice as much Ado-Cbl as Me-Cbl. Uptake by lymphocytes from patients with untreated pernicious anemia (PA) was greater than that by normal lymphocytes, but the proportions of Ado-Cbl and Me-Cbl synthesized by each were similar. Folic acid and methyltetrahydrofolate enhanced synthesis of Me-Cbl both in normal and in PA cells, while methotrexate and 5-fluorouracil depressed it. This depression was overcome by 5-formyltetrahydrofolate, suggesting that an uninterrupted folate cycle may play an important role in Me-Cbl synthesis.

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