Mechanism of vitamin B12 uptake by erythocytes.

Pitney, Beard, and Van Loon (2) and Ostrowski, Skarzynski, and Zak (3) reported in 1954 that vitamin B12 is bound primarily to a-globulin in normal serum. Pitney and his colleagues (2) also noted that p-globulin can bind B12 added in vitro, but they considered this as "free B12" because, unlike B12 bound to a-globulin, Euglena gracilis is able to utilize it without prior heat treatment. Miller (4) showed that B12 added to serum in vitro binds predominantly to a2and 8-globulin and that this fraction is nondialyzable. Hall and Finkler (5) confirmed the presence of two main B1,-binding globulins in serum, which Miller and Sullivan (6) and Weinstein, Weissman, and Watkin (7) had shown to be constituents of the seromucoid fraction. Little is known about the transfer of B12 from plasma to tissues. Callender and Lajtha (8) reported that partial maturation of megaloblasts in vitro can be produced by cyanocobalamin only when gastric juice or serum is present, thus suggesting the importance of a transferring protein. Miller, Raney, and Hunter (9) and Herbert (10) demonstrated that hog intrinsic factor promotes the uptake of B12 by rat liver slices; human serum has a similar effect (11 ). Cooper and Paranchych (12) found mouse Ehrlich ascites tumor cells and HeLa cells able to absorb B12 only in the presence