ABSTRACT

Absorption of vitamin B12 requires enzyme and acid hydrolysis in the stomach to liberate cobalamin (Cbl) from macromolecules, primarily protein. After digestive release, Cbl binds to salivary proteins (R-binders or haptocorrins), and is subsequently bound by the intrinsic factor secreted by gastric parietal cells.3 The intrinsic factor-vitamin B12 complex-then binds to receptors in the ileal mucosa and absorption occurs in the ileum through binding of Cbl in the presence of calcium with cell surface receptors and release of the intrinsic factor. After absorption, all circulating vitamin B12 is complexed with B12 plasma-binding proteins (transcobalamin I, II, or III) to form holoTCI, II, or III or with the B12 storage protein (haptocorrin) to form holohaptocorrin. Transcobalamin and haptocorrin complexes contain 20% and 80%, respectively, of total serum vitamin B12.3

Pernicious anemia evolves through abnormal absorption of vitamin B12 resulting from inadequate digestion, lack of necessary binding factors including Ca2+, lack of intrinsic factor due to lack of synthesis or autoimmune inactivation, absence of the delivery or storage proteins, and various other pathological states. Lack of sufficient dietary intake is usually not the cause of deficiency.4,5,6 Malabsorptive disorders cause about 50% of preclinical cases.6