Studies on the Transcobalamins

Abstract

Summary. Vitamin B12 absorbed from the gut is transported on all the vitamin B12 binding proteins (transcobalamins) and not primarily on Transcobalamin II. Absorbed vitamin B12 can still be detected on the vitamin B12 binding proteins after 10 days suggesting that the very rapid plasma clearance of the TCII‐vitamin B12 complex previously reported was probably due to damage to TCII prior to re‐injection. Vitamin B12 binder III is part of Transcobalamin I complex showing immunological identity with other binders in tissue fluids (R binders). Heparin given in vivo or in vitro prevented separation of Binder III from TCI and this effect was neutralized by protamine.

Role of Transcobalamins I, II and III in the Transfer of Vitamin B₁₂ to Human Bone Marrow Cells <i>in vitro</i>

“…As patients with an apparently complete deficiency of TCII suffer from a severe megaloblastic anaemia [14], and as patients with a partial deficiency of TCI seem to have normal erythropoiesis [5], it is generally believed that the B12 binder involved in the transfer of vitamin B12 to tissue cells is TCII and not TCI. This view is also consistent with the observation that vitamin B12 bound to TCI and TCIII clears more slow ly from the circulation than vitamin B,2 bound to TCII [8]. However, the above observations do not completely eliminate the possibility that TCI and TCIII participate in the transfer of some vitamin B12 to tissue cells, particularly as the cases of megaloblastic anaemia associated with TCII deficiency were also complicated by malabsorption of vitamin B12 [14] and by some atypical biochemical features [19].…”

“…The sera were saturated with S7Co-vitamin B12 by the addition of 2 ng of ! 'Co-cyanocobalamin (specific ac tivity 100-300 /tCi/,ug)/ml of serum, the unbound vitamin B,2 was removed by di alysis and the samples were then fractionated by a combination of DEAE-cellulosc chromatography and Sephadex G-200 filtration [4,8], Short-term marrow cultures were prepared using marrow aspirates from 7 pa tients with normoblastic erythropoiesis. The freshly-aspirated bone marrow was mixed with 5 ml Hanks' solution containing preservative-free heparin.…”

“…By contrast, transcobalamin II (TCII) is not a glycoprotein [2], is synthesised in the liver [6,7,23], and is an tigenically different from the 'R' binders [11,22], A third binder, termed transcobalamin III (TCIII), has recently been described in nor mal human serum [4,12,13]. This binder has the same molecular rad ius and antigenic characteristics as TCI [8] and may represent a fraction resulting from a partial separation of the 3 components of TCI with dif ferent iso-electric points [17]. In a recent study, W ickramasinghe and M offatt [25] showed that the uptake of serum-bound 37Co-cyanocobalamin by freshly-aspirated human bone marrow cells was mediated via an active, calcium-dependent process requiring the presence of cellular respiration and free sulphydryl groups.…”

A saturable high affinity binding site for transcobalamin II-vitamin B12 complexes in human placental membrane preparations.

“…B12 in human blood is carried by two major transport proteins (5), transcobalamin I (TCI) and transcobalamin II (TCII). TCI carries approximately 75% of the endogenous B12 in human plasma (6) and binds a small portion of B12 newly absorbed from the intestine (7). The functional role of TCI, however, remains unknown since a congenital deficiency of TCI in humans is asymptomatic anid does not result in reduced levels of vitamin B12 in tissues (8).…”

Transcobalamins I and II as natural transport proteins of vitamin B12.

“…Recently England et al (14) observed a third substance, which they refered to as TC III, carrying Bn in the early days after absorption. They postulated a transport system consisting of three plasma transport proteins, each picking up free B in the portal blood more or less in proportion to their unsaturated capacities.…”