Plasma Vitamin B12 Binding Proteins and Tissue Uptake

2 Plasma Vitamin B12 Binding Proteins and Tissue Uptake 

Vitamin B12 enters the circulation bound to transcobalamin II there is a relatively large amount of apotranscobalamin II in the circulation, and par-enterally administered vitamin is also protein-bound. The half-life of holo-transcobalamin II in plasma is of the order of 1.5 hours, and all cells have 

Altbougb transcobalamin II is tbe metaboUcaUy important pool of plasma vitamin B12, it accounts for only 10% to 15% of tbe total circulating vitamin. Tbe majority is bound to baptocorrin (also known as transcobalamin I). Tbe function of baptocorrin is not well understood it bas a relatively long balf-life (7 to 10 days), and does not seem to be involved in tissue uptake or intertissue transport of tbe vitamin. Altbougb genetic lack of transcobalamin 11 results in severe (and fatal) vitamin B12 deficiency, genetic lack of baptocorrin seems to bave no adverse effects. 

There is a third plasma vitamin B12 binding protein, transcobalamin III, which is rapidly cleared by the liver, with a plasma half-life of the order of 5 minutes. This seems to provide a mechanism for returning vitamin B12 and its metabolites from peripheral tissues to the liver, as well as for clearance of other corrinoids without vitamin activity, which may arise either from foods or the products of intestinal bacterial action and be absorbed passively from the lower gut. These corrinoids are then secreted into the bile, bound to cobalophUins. 

Considerably more intrinsic factor is secreted than is needed for the binding and absorption of dietary vitamin B12, which requires only about 1 % of the total intrinsic factor available. There is a considerable enterohepatic circulation of vitamin B12, variously estimated as between 1 to 9 /rg per day, about the same as the dietary intake. Like dietary vitamin B12 bound to salivary cobalophilin, the biliary cobalophUins are hydrolyzed in the duodenum, and the vitamin released binds to intrinsic factor, thus permitting reabsorption in the Ueum. Whereas cobalophUins and transcorrin III have low specificity, and wUl bind a variety of corrinoids, intrinsic factor orUy binds cobalamins, and only the biologicaUy active vitamin wiU be reabsorbed to any significant extent. 

---

In addition to the intrinsic factor, human tissues contain a number of proteins capable of binding vitamin B12 derivatives. These proteins include a plasma transcobalamin that facilitates B12 uptake in various tissues and a so-called R type group with unknown function whose binding capacities for vitamin B12... 

---