Vitamin B12 deficiency – A 21st century perspective | RCP Journals

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Fig 1.
Pictorial representation of the absorption of vitamin B₁₂ (cobalamin). Dietary vitamin B₁₂ is found in association with food proteins, and must be released on exposure to the low pH within the gastric lumen to facilitate absorption in the small bowel. Once liberated, vitamin B₁₂ is immediately bound by haptocorrin (transcobalamin I) and remains attached until proteolytic cleavage of the complex in the duodenum. Here, it is available to bind intrinsic factor (IF), a second carrier protein, synthesised by the parietal cells of the gastric mucosa. IF is necessary for uptake of vitamin B₁₂ in the terminal ileum. On traversing the brush border, vitamin B₁₂ dissociates from IF, and enters the circulation where it binds transcobalamin II or haptocorrin. Transcobalamin II and haptocorrin are responsible for delivery of cobalamin to peripheral tissues and the liver, respectively. Cbl = cobalamin; HC = haptocorrin; IF = intrinsic factor; PA = pernicious anaemia; PPI = proton pump inhibitor; TCII = trancobalamin II.
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Fig 2.
Intracellular metabolism of vitamin B₁₂. Following transport to peripheral tissues, free vitamin B₁₂ is generated. In the cytosol, vitamin B₁₂ (Cbl) is used as a cofactor by MS to react homocysteine with N⁵-MeTHF to produce methionine and THF. Synthesis of THF affords the downstream generation of purines and pyrimidines required for DNA and RNA synthesis, explaining the clinical features of deficiency. The only other vitamin B₁₂-dependent reaction is the conversion of methylmalonyl CoA to succinyl CoA by methylmalonyl CoA mutase, occurring in the mitochondria. Cbl = cobalamin; MCM = methylmalonyl-CoA mutase; MS = methionine synthase; N⁵-MeTHF = N⁵-methyltetrahydrofolate; TCII = transcobalamin II; TCII-R = transcobalamin II receptor; THF = tetrahydrofolate.

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