Effects of Vit B12 deficiency are most pronounced in rapidly dividing cells. How does B12 deficiency trap folate and result in megaloblastic anaemia?
To convert B12 to its active form (methylcobolamine) a methyl group is donated by folic acid (methyl tetrahydrofolate) which itself is converted yo tetrahydrofolate and is free to convert into other forms needed fot DNA synthesis (methylene tetrahydrofolate) In the absence of b12, tetrahydrofolate cant be generated because b12 was needed for the convesion of methyl-THF to THF Hence Methyl THF is the trapped form Methyl THF cant be used for DNA synthesis, it needs to be converted to THF before it csn form methylene THF.
Yeah, so 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.
