2015 Folate, Vitamin B12 and Inhibitors

Example questionTransport and intracellular retention of folates

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.

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LEUCOVORIN RESCUE

POLYGLUTAMINATION

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