B12 absorption and transport physiology (intrinsic factor, transcobalamin, terminal ileum)
Core concept
- Five hand-offs, and each one is a disease
- 1. Stomach - acid + pepsin free B12 from food protein
- Haptocorrin (R-binder, from saliva) binds it in the acid stomach
- Parietal cells secrete intrinsic factor
- 2. Duodenum - pancreatic proteases digest haptocorrin -> B12 handed to IF at alkaline pH
- 3. Terminal ileum - cubam receptor (cubilin + amnionless) endocytoses the IF-B12 complex
- *Calcium-dependent* - this is the step metformin blocks
- 4. Portal blood - B12 released and bound to transcobalamin II (holoTC)
- HoloTC is the metabolically active fraction delivered to marrow and tissue
- ~80% of circulating B12 is on haptocorrin and is inert - which is why serum B12 is a poor test
- 5. Cell - converted to methylcobalamin (cytoplasm) or adenosylcobalamin (mitochondrion)
3 more sections, plus exam facts
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