Transcobalamins I and II as natural transport proteins of vitamin B12

Abstract

There are two conflicting theories of how plasma vitamin B12 (B12) is transported in man: (a) by two distinct transport proteins, transcobalamins I and II (TC I and II), each having a specific role and time of function; and (b) by three active transport proteins, TC I, II, and III, that take up B12 randomly in proportion to the unsaturated amounts of each. To test these theories a man was given 1.12 μg, 229 μCi, of [57Co] B12 mixed with food. Blood samples were taken several times on the 1st day and at lengthening intervals up to day 51. The amount of TC II B12 measured in each sample by: gel filtration and by precipitation with (NH4)2SO4. Total serum R B12 was then separated into TC I and TC III by: (a) a single step anion exchange system and (b) isoelectric focusing (IEF). As the B12 was being absorbed, 92-95% of that in venous blood was carried by TC II. Absolute and percentage transport by TC II declined sharply during the first 24 hr; between days 7 and 51 20-33% of the label was on TC II, and the rest was carried by R type binders. Absolute transport by TC I did not reach a maximum until after day 1 and before day 3. Transport by an α2 R type binder, TC III, could not be demonstrated. TC I was isoelectrically heterogenous, with the components focusing between pH 2.9 and 3.35. It was concluded that (a) TC II is the dominant carrier of B12 immediately after absorption; (b)maximum transport by TC I requires the passage of time after absorption; (c) after the absorbed B12 reaches equilibrium with the total body B12, about one fourth of the plasma B12 is carried by TC II and three fourths by TC I; and (d) TC I and TC II are the only functional transport proteins of plasma B12.