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
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?
*can be caused by folic acid deficiency in alcoholics