The distribution of endogenous cobalamin among cobalamin-binding proteins in the blood in normal and abnormal states.

Our information about cobalamin transport in the blood is largely based on studies of unsaturated cobalamin-binding proteins. Therefore, the distribution of endogenous cobalamin among these proteins was examined. Normally, R binder (transcobalamin I) carries most of the cobalamin circulating at any given moment, but the proportion varies greatly. Transcobalamin II carries a larger fraction of the cobalamin present in portal vein blood than in hepatic and axillary vein blood. In disease, transcobalamin II occasionally holds the bulk of the vitamin present in peripheral blood. Such was observed in three patients showing quantitative changes of unsaturated binder (either diminished R binder or increased transcobalamin II), but in two cases of chronic liver disease this was independent of unsaturated transcobalamin levels. Four patients with low serum cobalamin levels maintained normal distribution, indicating proportional cobalamin depletion from both binder pools. Small amounts of vitamin were attached in many sera to minor binders, and occasionally seemed to circulate free. These results demonstrate that assumptions that cobalamin is always attached largely to transcobalamin I are not warranted. Cobalamin distribution appears to be governed by many factors, of which the amounts of the binding proteins is only one.