Synthesis of cobalamin coenzymes by human lymphocytes in vitro and the effect of folates and metabolic inhibitors.
The uptake of 57Co-cyanocobalamin (CN-Cbl) and its conversion to 5-deoxyadenosylcobalamin (Ado-Cbl), methylcobalamin (Me-Cbl), and hydroxocobalamin (OH-Cbl) has been studied in phytohemagglutinin (PHA)-transformed lymphocytes from normal subjects and patients with 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 hr incubation. Ado-Cbl was the major cobalamin formed, and after 72 hr 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.
D000963:Antimetabolites / Q000494:pharmacology*; D003038:Cobamides / Q000096:biosynthesis*; D005492:Folic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology; D014805:Vitamin B 12 / Q000378:metabolism
D000963:Antimetabolites; D003038:Cobamides; D037102:Lectins; D005492:Folic Acid; D014805:Vitamin B 12; D008727:Methotrexate