Diagnostic and Prognostic Values of Measurement of Serum Vitamin B12-Binding Proteins

T FIAT VITAMIN B12 IN SERUM is l)ound to protein14 has been known since shortly after the isolation of the vitamin. Endogenous vitamin B12 (which may be mainly methyl-Bi2) is bound primarily to an a1-globulin 2.6-10 hut vitamin B12 added to serum in vitro hinds primarily to -globuun (presumably because B12-binding a-globulin is normally almost saturated with endogenous vitamin B12).61#{176} hall and Finkler’1 have reported that when vitamin B12 is fed by mouth or injected, it attaches first to a-globulin, and, during the ensuing 24 hr., transfers to a-globulin. Our preliminary studies12’13 suggest an alternate explanation; namely, that ingested or injected vitamin B12 attaches both to aand /3-globulin B12-binding proteins, but that which is attached to a-globulin is delivered to tissues within twenty-four hours whereas that attached to aglobulin is retained by the serum. Our studies suggest that the two B1 binding globulins act in relation to B12 much as the two binding proteins for copper act in relation to that mineral. Ingested copper, after absorption, is picked up by albumin and delivered to the liver, where it is “packaged” in ceruloplasmin to be circulated therein as stored copper.14 Thus, albumin is a transport protein for copper, and ceruloplasmin is a copper-storage protein. While both B12-binding globulins may deliver the vitamin to reticulocytes13.1 and liver1 (and presumably other tissues as well, including tumor cells16), our studies suggest that the B12-binding /3-globulin is primarily a transport protein,13 whereas the B12-binding a-globulin functions mainly to conserve the vitamin. B12-binding a-globulin has a greater affinity for B12 and retains the vitamin more tenaciously than does the B12-binding f3-globulin,’2 doling it out sparingly when a short supply necessitates conservation of availal)le vitamin. Since normally B12-binding a-globulin is almost saturated with the vitamin, and B2-binding a-globulin is totally unsaturated, in the normal situation absorbed vitamin B12 attaches primarily to n-globulin and is deli cred to tissues. In the B1 -deficient state, B12-binding a-globulin is relatively