Overview
Clinical Meaning
Vitamin B12 (cobalamin) absorption is a complex, multi step process requiring intact gastric, pancreatic, and ileal function.
PNP-PC
PNP-PC
Vitamin B12 (cobalamin) absorption is a complex, multi-step process requiring intact gastric, pancreatic, and ileal function. Dietary B12, found exclusively in animal products, is bound to food proteins and released in the stomach by pepsin and hydrochloric acid. Free B12 binds to R-binders (haptocorrin) secreted by salivary glands and gastric mucosa. In the duodenum, pancreatic proteases digest R-binders, transferring B12 to intrinsic factor (IF), a glycoprotein produced by gastric parietal cells. The B12-IF complex travels to the terminal ileum where it binds to the cubilin-amnionless receptor complex (cubam) on ileal enterocytes and is internalized by receptor-mediated endocytosis. Within enterocytes, B12 is released from IF, binds to transcobalamin II (TCII), and enters the portal circulation. TCII delivers B12 to tissues via TCII receptors. Only 20% of circulating B12 is bound to TCII (holotranscobalamin, the biologically active fraction); the remaining 80% is bound to haptocorrin (biologically inert). Pernicious anemia, the most common cause of severe B12 deficiency, results from autoimmune destruction of gastric parietal cells with loss of IF production and concurrent achlorhydria. Neurologically, B12 deficiency causes subacute combined degeneration: demyelination of...
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