Folate is important in the production of various building blocks necessary for the production of biologic macromolecules.  By combining with carbon moieties, tetrahydrofolate (THF) becomes methelenetetrahydofolate.  This molecule is then able to donate carbon moieties to form purines, dTMP, and methionine. Of note, Vitamin B12 is also a cofactor in the production of methionine. THF is the resulting molecule after donation of carbon moieties except in the synthesis of  dTMP from dUMP.  DHF (dihydrofolate) results from this reaction.  DHF reductase must act on DHF to participate in reactions again. The two metabolically active forms of Vitamin B12 are Methycobalamin and Adenosylcobalamin.  The former is important in methionine synthesis.  Methionine is necessary for the production of choline phospholipids.  Adenosylcobalamin is necessary to convert methylmalonyl CoA to succinyl-CoA.  Interruption of this reaction eventually leads to nonphysiologic fatty acid production and abnormal neuronal lipid production. B12 deficiency also leads to folate metabolism derangement.  Tissue folate levels are reduced in the setting of Vitamin B12 deficiency through a complicated biochemical pathway.  This is known as the “folate trap hypothesis” and explains why large doses of folate will help the hematological manifestations.  The mechanism of the neurologic manifestations remains independent of folate metabolism.
Macrocytic anemia pathophysiology
Polycythemia pathophysiology
Iron deficiency anemia pathophysiology
Hemolytic anemia pathophysiology
Hemosiderosis pathophysiology
Sideroblastic anemia pathophysiology
Macrocytic anemia risk factors
Cryoglobulinemia risk factors