Binding of cobalamin analogs to intrinsic factor-cobalamin receptor and its prevention by R binder.
It is now known that nonphysiological cobalamin analogs exist in the gastrointestinal tract, but their metabolic behavior is unclear. In this study, [57Co]cobinamide was used to study its affinity to hog intrinsic factor-cobalamin (IF-Cbl) receptor which has no species specificity against human IF-Cbl receptor, and its relation to human saliva R binder. Cobinamide was prepared from [57Co]cyanocobalamin and separated by paper chromatography. Human IF-Cbl complex was bound to IF-Cbl receptor but free cyanocobalamin was not. Although R binder-cobinamide was not bound to the IF-Cbl receptor, free cobinamide was bound to the IF-Cbl receptor to a significant extent (about one-half of IF-cyanocobalamin binding to the IF-Cbl receptor). We then investigated the binding of cobinamide to R binder and trypsin-treated R binder. Association constant of cobinamide binding to the IF-Cbl receptor was 1.0 X 10(9) M-1 which was much lower than that of cobinamide binding to trypsin-treated R binder and to untreated R binder. Further study indicated that cobinamide binding to the IF-Cbl receptor was blocked by the addition of R binder and also by trypsin-treated R binder. We conclude that one of the roles of R binder is to prevent binding of free cobalamin analogs to the IF-Cbl receptor in the gut.
D003038:Cobamides / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014155:Transcobalamins / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000378:metabolism
D003038:Cobamides; D011956:Receptors, Cell Surface; D014155:Transcobalamins; C029486:intrinsic factor-cobalamin receptor; C017142:cobinamide; D014357:Trypsin; D014805:Vitamin B 12