2015 Folate, Vitamin B12 and Inhibitors

Critical Facts IconCRITICAL FACTS
(if med school is a Minnesota forest with millions of trees, these are the red pines)

  1. Folate and vitamin B12 are required for DNA synthesis and for maintenance of neurons and red blood cells. Folate is a carbon donor in thymidylate and purine synthesis, as well as amino acid metabolism. Vitamin B12 is a critical cofactor in the generation of tetrahydrofolate from liver stores of methyltetrahydrofolate.

  2. Reduced expression or mutation of the reduced folate carrier (RFC) is a cause of primary resistance to low doses of folate inhibitors (such as METHOTREXATE). Both cancer cells and bacteria (esp. Pneumocystis jirovecii - an AIDS-associated infection) can exhibit resistance.  High doses of MTX are used to overcome this resistance, and subsequent administration of LEUCOVORIN allows normal cells with functional RFC to bypass the drug-induced inhibition of dihydrofolate reductase.  This is the fundamental principle underlying rescue therapy.

  3. Folate and vitamin B12 are dietary essentials.  Deficiency of either compound prevents DNA synthesis, and has catastrophic effects on rapidly growing cells and on neurons.  The most prominent clinical sign of deficiency is megaloblastic anemia.

  4. TRIMETHOPRIM (a folic acid inhibitor) is typically combined with SULFAMETHOXAZOLE (which blocks dihydropteroate synthetase).  These drugs act synergistically, blocking successive steps in the folate synthesis pathway in bacteria.

Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 4-may-15 9:28 PM