Vitamin B12(Cobalamin) Absorption

Cobalamin, or vitamin B₁₂, is synthesized only by microorganisms, not by mammalian cells. Only bacteria and archaea have the enzymes required for its synthesis; neither fungi, plants, nor animals (including humans) are capable of producing vitamin B₁₂. Although many foods (Animal products: meat, fish, shellfish, eggs, and (to a limited extent) milk) are a natural source of B₁₂ because of bacterial symbiosis. The vitamin is the largest and most structurally complicated vitamin and can be produced industrially only through bacterial fermentation-synthesis.

Cobalamin is not present in vegetables or fruit. Therefore, strict vegetarians are at risk of developing dietary cobalamin deficiency

Cobalamin’s primary function is to serve as a coenzyme for homocysteine (See schema below): methionine methyltransferase, which transfers a methyl group from methyltetrafolate to homocysteine, thereby converting homocysteine to methionine. Methionine is an essential amino acid and in an altered form serves as an important donor of methyl groups in several important enzymatic reactions. If cobalamin is deficient and methionine levels fall, then the body converts its stores of intracellular folate (e.g., PteGlu1, THF, 5,10-methylene THF) into N 5 -methyl THF in an effort to produce more methionine. As a result, 5,10-methy-lene THF (the form of folate needed for DNA synthesis) falls, an effect that explains why folate and cobalamin deficiencies cause identical hematologic abnormalities (i.e., megaloblastic anemia). In addition, cobalamin deficiency causes various neurologic and psychological abnormalities that are not part of the syndrome of folate deficiency.

Cobalamin reaches the stomach bound to proteins in ingested food. In the stomach, pepsin and the low gastric pH release the cobalamin from the ingested proteins. The now-free cobalamin binds to haptocorrin (formerly known as “R” type binder), a glycoprotein secreted by the salivary and gastric glands. The parietal cells of the stomach secrete a second protein, intrinsic factor (IF), crucial for the absorption of cobalamin. However cobalamin and IF do not interact in the acidic milieu of the stomach. Rather, gastric acidity enhances the binding of cobalamin to haptocorrin. Vitamin B₁₂ is structurally very sensitive to the hydrochloric acid found in the stomach secretions, and easily denatures in that environment before it has a chance to be absorbed by the small intestine. Vitamin B₁₂ attaches haptocorrin. When this cobalamin-haptocorrin complex reaches the duodenum, the haptocorrin is degraded by pancreatic proteases. After the release of cobalamin from the cobalamin-haptocorrin complex in the proximal small intestine-made alkaline by the secretion of HCO₃^- from the pancreas and duodenum—both dietary cobalamin and cobalamin derived from bile bind to IF. The cobalamin-IF complex is highly resistant to enzyme degradation.

The next step in the absorption of cobalamin is the binding of the cobalamin-IF complex to specific receptors on the apical membranes of enterocytes in the ileum. Cobalamin without IF neither binds to ileal receptors nor is absorbed. The binding of the cobalamin-IF complex is selective and rapid and requires Ca²⁺, but it is not energy dependent. The enterocyte next internalizes the cobalamin-IF complex in a process that is energy dependent but has not been well characterized

Inside the cell, cobalamin and IF dissociate; lysosomal degradation may play a role here. Within the enterocyte, cobalamin binds to another transport protein—transcobalamin II—which is required for cobalamin’s exit from the enterocyte. The cobalamin exits the ileal enterocyte across the basolateral membrane bound to transcobalamin II, possibly by an exocytotic mechanism. The transcobalamin II-cobalamin complex enters the portal circulation, where it is delivered to the liver for storage and for secretion into the bile