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Vitamin B12 metabolism

Vitamin B12 is released from its food-binding proteins by the action of gastric acid and proteolytic enzymes in the stomach. It is then captured by haptocorrin (transcobalamin I), an R-binder protein in the saliva and stomach. In the upper small intestine, pancreatic enzymes and an alkaline pH degrade the haptocorrin-B12 complex. The free vitamin is then captured by intrinsic factor (IF), another B12 binding protein. In the terminal ileum, the IF-B12 complex binds to IF receptors on the membrane surface of enterocytes and is then transferred through the ileal membrane. B12 is subsequently released in the enterocytes and transferred to a third binding protein, transcobalamin II (TC). TC is synthesized within the enterocytes and is the only binder that can deliver vitamin B12 into cells via TC-receptor. The B12-TC complex, named holotranscobalamin (holoTC) (1), is released into the portal circulation, arrives the blood circulation and circulates until it is taken up by the peripheral cells. B12 bound to TC is recognized by TC-receptors that are expressed by all cell types. A maximum of 30% of circulating B12 is bound to TC, which represents metabolically active vitamin B12 (2). The remaining part of B12 (about 70 – 80%) is bound to haptocorrin and is called holohaptocorrin (holoHC).

The receptor-mediated absorption of B12 is a saturable process and a maximal amount of 3 μg of the vitamin per meal is thought to be internalized via this pathway. A considerable amount of B12 is secreted into the bile. Two-thirds of the secreted B12 in the bile is reabsorbed in the ileum. The liver contains most of the B12 in the body (2 – 3 mg) (3). The kidney and the brain also accumulate B12. Vitamin B12 is excreted into urine and this can be reabsorbed in the proximal tubules via a specific receptor (megalin/cubilin). The major route by which B12 is lost from the body is through the feces.


1.     Carmel R. The distribution of endogenous cobalamin among cobalamin-binding proteins in the blood in normal and abnormal states. Am J Clin Nutr 1985;41:713-9.
2.     Hall CA. The carriers of native vitamin B12 in normal human serum. Clin Sci Mol Med 1977;53:453-7.
3.     Markle HV. Cobalamin. Crit Rev Clin Lab Sci 1996;33:247-356.