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Flashcards in Folate & B12- Fitz Deck (15):


reduced form of folate

provides folate to normal tissues, as mech to surpass inhibition of DHFR (MTX therapy)

Some cancer cells cannot uptake because do not have functional REDUCED FOLATE CARRIER needed for uptake



Competitive inhibitor of Dihydrofolatreductase inhibitor


What is a source of primary resistance of methotrexate?

Reduced expression or mutation of the RFC.

Need to give higher dose MTR, also administer Leucovorin, to decrease toxicity to normal cells (Leucovorin rescue)


Describe rescue therapy in regards to MTX administration

Reduced expression/mutation in RFC of cancer cells (primary resistance to low does MTX)

Need to increase MTX dosage to overcome resistance

Also give leucovorin to allow normal cells with functional RFC to bypass drug induced inhibition of DHFR


What are the two major folate transporters?

Reduced folate carrier (RFC)

Folate Receptor - only on some tissues, transports folates when they are present at very low concentrations


What makes some leukemias and gynecological and epithelia cancers more sensitive to folate inhibitors?

Over expression of folate receptor


Adding of what molecule causes more potent binding to folate-dependent enzymes, and prevents the drug from leaving the cell?

Adding of polyglutamates by FPGS


Mechanism of action of Pemetrexed and Pralatrexate?

Antagonists of thymidylate synthase and purine synthesis


Why is polyglutamating considered selective toxicity?

Because tumor cells are more capable of polyglutamating, this increases the concentration of the drug in CANCER cells, rather than our normal cells


Increased homocysteine levels are diagnostic of what?

Vitamin B12 deiciency


What are the major funcitons of Folate and Vit. B12?

**Required for DNA synthesis and maintenance of neurons and RBCs


Folate Reactions

Carbon donor in thymidylate and purine synthesis


Vit B12 Reactions

Critical cofactor in the generation of THF from livers stores of methylTHF


What is the most prominent sign of Folate and B12 deficiency?

Megaloblastic Anemia

*can be caused by folic acid deficiency in alcoholics


MOA of Trimethoprim and Sulfamethoxazole?

Selective bacterial folic acid inhibitor

Sulfa- blocks dihydropteroate synthase

Act synergistically