Vitamin B12: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Vitamin B12: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Vitamin B12 is a vitamin with a cobalt atom at its centre. The body uses it in two active forms: as cofactor of methionine synthase in the cytosol and of methylmalonyl-CoA mutase in mitochondria.

The pathway step by step

1. B12 in food → B12 + haptocorrin Pepsin · Stomach acid Stomach acid and the enzyme pepsin release B12 from protein. It binds at once to haptocorrin, a shielding protein from saliva. Source 1
2. B12 + haptocorrin → B12 + intrinsic factor Pancreatic proteases Pancreatic enzymes break down haptocorrin. B12 now binds to intrinsic factor, which is made by the parietal cells of the stomach. Source 1
3. B12 + intrinsic factor → Into the gut cell Cubam receptor · Calcium The receptor cubam recognises the complex of B12 and intrinsic factor. This step needs calcium. Source 1, 5
4. Into the gut cell → Holotranscobalamin · Transcobalamin The gut cell releases B12 bound to transcobalamin into the blood. This form is called holotranscobalamin; cells can absorb it. Source 1
5. B12 in the cell → Methylcobalamin Active form in the cytoplasm. It is the cofactor of methionine synthase. Source 3
6. B12 in the cell → Adenosylcobalamin Active form in the mitochondrion. It is the cofactor of methylmalonyl-CoA mutase. Source 4
7. Homocysteine → Methionine Methionine synthase · 5-methyl-THF (folate) Methionine synthase transfers a methyl group from 5-methyltetrahydrofolate to homocysteine, forming methionine again. Source 3
8. Methionine → SAM MAT · ATP Methionine and ATP form S-adenosylmethionine, the main methyl group donor of the cell. Source 3
9. SAM → Methylation Methyltransferases Methyltransferases transfer methyl groups from SAM to DNA, proteins and other molecules; this forms homocysteine again. Source 3
10. Methylmalonyl-CoA → Succinyl-CoA MM-CoA mutase Methylmalonyl-CoA mutase converts methylmalonyl-CoA into succinyl-CoA; adenosylcobalamin is the cofactor. Source 4
11. Succinyl-CoA → Citric acid cycle Succinyl-CoA is an intermediate of the citric acid cycle, the central hub of energy metabolism. Source 4

Cofactors in this pathway

• Folate — As 5-methyl-tetrahydrofolate it supplies the methyl group for methionine synthase Source 3In the ORY catalogue as a laboratory value: Folsäure
• Calcium — The Cubam receptor takes up the B12–intrinsic factor complex only with calcium Source 1, 5
• Gastric acid — Together with the enzyme pepsin it releases B12 from dietary protein Source 1
• Methionine — Formed at methionine synthase and, with ATP, builds the methyl group donor SAM Source 3In the ORY catalogue as a laboratory value: Methionin

What acts on this pathway

• Acid-reducing drugs — Less stomach acid can reduce the release of B12 from dietary protein. The product information for proton pump inhibitors mentions this link. Source 6
• Metformin — Lower B12 levels have been described with metformin. In one study, the reduced uptake was reversed by additional calcium — a pointer to the calcium-dependent step. Source 5

Sources

1. Nielsen MJ, Rasmussen MR et al. Vitamin B12 transport from food to the body's cells — a sophisticated, multistep pathway. Nat Rev Gastroenterol Hepatol 2012 · PubMed 22547309
2. Quadros EV, Nakayama Y et al. The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin. Blood 2009 · PubMed 18779389
3. Froese DS, Fowler B et al. Vitamin B12, folate, and the methionine remethylation cycle — biochemistry, pathways, and regulation. J Inherit Metab Dis 2019 · PubMed 30693532
4. Takahashi-Iñiguez T, García-Hernandez E et al. Role of vitamin B12 on methylmalonyl-CoA mutase activity. J Zhejiang Univ Sci B 2012 · PubMed 22661206
5. Bauman WA, Shaw S et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000 · PubMed 10977010
6. US prescribing information Pantoprazole (DailyMed), section 5.7 Cyanocobalamin (Vitamin B-12) Deficiency · Prescribing information

Related pathways

• Methylation: methionine and homocysteine — homocysteine
• Threonine — methylmalonyl-coa
• Branched-chain amino acids — succinyl-coa
• Citric acid cycle — succinyl-coa
• Glutathione — homocysteine

As of 2026-09-16. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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