Cobalamin (vitamin B12) !

Vitamin B12 contains cobalt and only two enzymes use it, but its lack causes megaloblastic anaemia and spinal cord damage.

Updated 2026-11-01

Key facts

Two active forms: methylcobalamin (methionine synthase: homocysteine → methionine) and adenosylcobalamin (methylmalonyl-CoA mutase: methylmalonyl-CoA → succinyl-CoA).
Found only in animal foods: vegans need fortified foods or supplements.
Its absorption needs intrinsic factor from gastric parietal cells and the terminal ileum.
The liver holds stores for several years, so deficiency develops slowly.

Commercial and lab forms: cyanocobalamin and hydroxocobalamin; the body converts them into methyl- and adenosylcobalamin.
Absorption path: acid and pepsin free it from proteins; it binds haptocorrin (saliva); in the duodenum pancreatic proteases release it; it binds intrinsic factor; the complex enters through the cubam (cubilin) receptor in the terminal ileum; in blood it travels with transcobalamin II.
Methionine synthase: B12 takes the methyl from 5-methyl-THF and passes it to homocysteine. Without B12, folate is 'trapped' as 5-methyl-THF (the folate trap) and THF runs short for DNA: megaloblastic anaemia.
Methylmalonyl-CoA mutase: without B12, methylmalonic acid and propionate accumulate and disturb myelin synthesis: subacute combined degeneration of the dorsal and lateral columns.
Causes of deficiency: pernicious anaemia (autoimmune), gastrectomy or bariatric surgery, atrophic gastritis in older adults, ileal resection or disease (Crohn), metformin, long-term proton pump inhibitors, vegan diet, nitrous oxide, fish tapeworm (Diphyllobothrium latum).
Excess: not toxic; a very high serum B12 without supplements can point to liver or myeloproliferative disease.
Lab: serum B12 (low), methylmalonic acid and homocysteine (both high, more sensitive), blood count with high MCV and hypersegmented neutrophils; antibodies to intrinsic factor and to parietal cells.

Also called: Vitamin B12, Cyanocobalamin, Methylcobalamin, Adenosylcobalamin, Hydroxocobalamin

Nerve damage (paraesthesia, loss of vibration and position sense, ataxia, dementia) can appear without anaemia and become permanent if treatment is delayed.
When intrinsic factor is missing, B12 is replaced intramuscularly or with high oral doses, a little of which is absorbed by diffusion.
Years of metformin and long-term proton pump inhibitors lower B12: it is monitored in people with diabetes and neuropathy.

Think of the answer, then tap the question to see it.

Which two reactions depend on vitamin B12?

Methionine synthase (homocysteine → methionine, with methylcobalamin) and methylmalonyl-CoA mutase (→ succinyl-CoA, with adenosylcobalamin).

What is the folate trap?

Without B12, 5-methyl-THF cannot give up its methyl and accumulates; THF runs short for thymidylate and megaloblastic anaemia follows.

Why does B12 deficiency damage the spinal cord while folate deficiency does not?

Failure of methylmalonyl-CoA mutase builds up methylmalonic acid, which disturbs myelin in the dorsal and lateral columns.

Where is vitamin B12 absorbed and what does it need?

In the terminal ileum, bound to intrinsic factor made by the stomach's parietal cells.

Which test is most sensitive for B12 deficiency?

Serum methylmalonic acid, which rises even when B12 is borderline low.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Vitamin B12: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Vitamin B12 deficiency anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Vitamin B12 level: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Methylmalonic Acid (MMA) Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2026); Imerslund-Gräsbeck syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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