Normal pathway of B₁₂ absorption and cellular uptake. Food B₁₂ is released in the stomach and binds to salivary HC. In the small intestine, food B₁₂ and biliary B₁₂ are released from HC by pancreatic proteases and bind to intrinsic factor (IF). The IF-B₁₂ complex then binds to the cubam (Cubilin [Cub]–amnionless [Amn]) receptor in the terminal ileum for internalization and release to plasma where it is bound by TC. TC delivers B₁₂ to the TC receptor (CD320) on cells, and following release in the cell, B₁₂ is reduced and converted to adenosylcobalamin in the mitochondria and methylcobalamin in the cytosol, where they serve as cofactors for the 2 B₁₂-dependent reactions. CoA, coenzyme A; THF, tetrahydrofolate. Professional illustration by Patrick Lane, ScEYEnce Studios.