The uptake of vitamin B12 by human lymphocytes and the relationships to the cell cycle.
The phase of the cell cycle permitting transcobalamin II (TC II) mediated entry of cobalamin (Cbl) into human lymphocytes was determined under several conditions. (1) Little was taken up by resting peripheral blood lymphocytes (PBL). (2) Uptake was enhanced by stimulation of PBL by culture with a mitogen. (3) This increase in capacity for uptake took place simultaneously during 3 days of culture with the increase in capacity to synthesize DNA. (4) Hydroxyurea inhibited both DNA synthesis and TC II-Cbl uptake. (5) As culture was prolonged and the cells passed beyond the phase of most active division, DNA synthesis and Cbl uptake declined sharply. (6) The increased capacity to take up Cbl after stimulation was determined, at least in part, by increased receptor activity for TC II-Cbl. (7) Internalization of the Cbl was also increased. (8) Simultaneously with the increasing DNA synthesis, the cells increased in the activity of the Cbl-dependent methionine synthetase (MS). (9) MS activity subsequently fell during longer culture. Thus PBL can take in Cbl only during a narrow "window" in the cell cycle. This window is associated with the period of most active DNA synthesis and at a time when one coenzyme of Cbl, MeCbl, is the most active.
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000328:Adult; D002453:Cell Cycle; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007223:Infant; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014805:Vitamin B 12 / Q000378:metabolism* / Q000502:physiology; D014806:Vitamin B 12 Deficiency / Q000503:physiopathology
D004247:DNA; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12; D006918:Hydroxyurea