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Pathogenesis of vitamin B12 deficiency
Last reviewed: 06.07.2025
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In plasma, vitamin B 12 is present in the form of coenzymes - methylcobalamin and 5'-deoxyadenosylcobalamin. Methylcobalamin is necessary for normal hematopoiesis, namely for the synthesis of thymidine monophosphate, which is part of DNA, and the formation of tetrahydrofolic acid. Disruption of thymidine formation due to vitamin B 12 deficiency leads to disruption of DNA synthesis, slowing down of normal processes of maturation of hematopoietic cells (lengthening of the S phase), which is expressed in megaloblastic hematopoiesis. Not only erythropoiesis suffers, but also granulocyto- and thrombocytopoiesis. Thus, the basis of hematopoiesis disruption due to vitamin B 12 deficiency is the mechanism of delayed normal cell maturation. 5'-deoxyadenosylcobalamin is involved in the metabolism of methylmalonic acid (an intermediate product of fatty acid metabolism) into succinic acid. With a deficiency of vitamin B 12, the content of methylmalonic acid in the blood increases and it appears in the urine.
Cobalamin deficiency causes neurologic dysfunction due to patchy demyelination of gray matter in the brain, spinal cord, and peripheral nerves. The cause of demyelination is not fully understood. It is possible that inhibition of methylmalonyl-CoA mutase inhibits the metabolism of odd-carbon fatty acids, resulting in the incorporation of abnormal fatty acids into myelin. These abnormal acids have been detected in peripheral nerve biopsies in patients with cobalamin deficiency. Methionine deficiency may contribute to neurologic dysfunction by disrupting the production of choline-containing phospholipids.