Cobalamin, also known as Vitamin B12 is a B vitamin, which is a water-soluble vitamin of animal food origin and that it is unique in being stored significantly in the body. Cobalamin is the only use for cobalt in humans. Bacteria make vitamin B12 for cows, which is why they can be cobalt deficient, whereas humans cannot. However, 1μg per day of dietary intake is needed.
Vitamin B12 needs an extrinsic factor (found in the liver) and an intrinsic factor (a protein secreted by the stomach). Pernicious anemia is a form of vitamin B12 malabsorption and caused by defective secretion of intrinsic factor, which is most often related to autoimmune destruction of parietal cells in the stomach, which are responsible for the synthesis of intrinsic factor. Two important biochemical reactions involving B12 are the conversion of homocysteine to methionine (which also requires folate) and the conversion of methylmalonic acid (Methylmalonyl CoA) to succinic acid (Succinyl CoA).
Given that vitamin B12 is involved in the recycling of tetrahydrofolate cofactors, deficiency of B12 can cause the symptoms of folate deficiency. In B12 deficiency, usable folate becomes trapped as Methyl TFA, which prevents the other forms of TFA from being available for DNA synthesis. Because all of the other reactions are reversible, they will equilibrate, producing more and more 5,10-methylene THF (whose equilibrium goes towards 5-methyl THF. Folate supplementation can alleviate the "trap".
- Neurological symptoms of B12 deficiency likely result from problems with the metabolism of methyl groups and maybe methylmalonate.
B12 deficiency is unique in causing peripheral neuropathies. This can happen because neurons are particularly sensitive to decreases in methylation due to the requirements of maintaining heavily methylated phospholipids in myelin, since homocysteine may be toxic to neurons or neuronal function. An accumulation of methylmalonyl CoA in B12 deficiency may also be responsible for neuronal degeneration, since it competitively inhibits malonyl CoA in fatty acid biosynthesis. This leads to myelin degeneration as a consequence of rapid myelin turnover.
Folate administration for the correction of megaloblastic anemia can mask an underlying B12 deficiency, which may proceed to neurologic dysfunction. While folate supplementation will help correct megaloblastic anemia, it will not correct an accumulation of methylmalonyl CoA due to B12 deficiency, and so neurological symptoms result. If malabsorption continues, further clinical followup is necessary, as pernicious anemia is to be suspected.