The pathogenesis of vitamin B12 deficiency

In plasma, vitamin B _{12 is} present in the form of coenzymes - methyl cobalamin and 5'-deoxyadenosyl cobalamin. Methylcobalamin is necessary to ensure normal hematopoiesis, namely for the synthesis of thymidine monophosphate, which is part of the DNA, and the formation of tetrahydrofolic acid. Violation of the formation of thymidine with a deficiency of vitamin B ₁₂ leads to a violation of the synthesis of DNA, slowing down the normal processes of maturation of hemopoietic cells (lengthening phase S), which is expressed in megaloblastic hematopoiesis. Not only erythropoiesis suffers, but also granulocyte and thrombocytopoiesis. Thus, the basis of disorders of hematopoiesis at deficiency of vitamin B ₁₂ is the mechanism delay normal cell maturation. 5'-deoxyadenosylcobalamin is involved in the metabolism of methylmalonic acid (an intermediate product of the metabolism of fatty acids) into succinic acid. With a deficiency of vitamin B ₁₂, the blood content of methylmalonic acid increases and it appears in the urine.

Deficiency of cobalamin causes neurologic disorders due to spotted demyelination of gray matter in the brain and spinal cord and peripheral nerves. The cause of demyelination is not completely clear. Perhaps the inhibition of methylmalonyl-CoA mutase inhibits the metabolism of fatty acids containing an odd number of carbon atoms, resulting in the introduction of abnormal fatty acids into myelin. These abnormal acids were detected with peripheral nerve biopsy in patients with cobalamin deficiency. The appearance of neurological disorders may be promoted by a methionine deficiency due to a disruption in the production of cholin-containing phospholipids.