B12 deficiency aka Pernicious anemia and Folate Trap Hypothesis.
Tetrahydrofolate (THF) is the functional form of Folic Acid which receives and transfers one carbon fragments to the intermediates in synthesis of purines and pyrimidines for DNA. Deficiency of THF results in diminished synthesis of neucleotides which leads to inability of rapidly dividing cells to make DNA and therefore inability to divide, such cells include RBC precursor cells aka Megaloblasts in bone marrow which are released in the blood, they are unusually large, structurally abnormal, immature RBCs. Methyl Cobalamine is the active form of Vit B12 which acts as an enzyme for remethylation of Homocysteine to Methionine. Here, methyl group for remethylation of Cobalamine and hence Homocystein is provided by methyl-THF. When Vit-B12 is absent, these reactions can not occur and hence folic acid gets trapped in its methylated form which accumulates and the other functional forms decrease, therefore barring the rapidly dividing cells from maturation and division. Thus, Vit-B12 deficiency leads to deficiency of THF forms needed in DNA synthesis (by trapping it in methylated form), resulting in megaloblastic anemia.
