Flashcards in Folate, B12, and Inhibitors - Fitz Deck (19)
1
What is the first symptom of a vitamin B12 or Folate deficiency?
Megaloblastic Anemia
2
What cell processes is folate a carbon donor to?
Thymidylate Synthesis
Purine Synthesis
Amino Acid Metabolism
3
Vitamin B12 is a cofactor in the generation of what?
Tetrahydrofolate (from methylTH4)
Methylmalonyl CoA to Succinyl CoA
4
What is one cause of primary resistance in low doses of folate inhibitors?
Reduced expression of the Reduced Folate Carrier (RFC)
5
How does Leucovorin function?
Allows normal cells with functional RFC to overcome the drug induced inhibition of dihydrofolate reductase
6
How does Trimethoprim-Sulfamethoxazole work?
Trimethoprim = folic acid inhibitor
Sulfamethoxazole = blocks dihydropteroate synthetase
=>Blocks Folate Synthesis pathway via bacterial dihydrofolate reductase
7
What laboratory finding is diagnostic of a Vitamin B12 Deficiency?
Homocysteine (converted to methionine via B12 catalysis)
8
How is leucovorin used in rescue therapy?
Replaces folate by being converted to TH4
9
What are the naturally occuring forms of Vitamin B12?
Adenosylcobalamin
Methylcobalamin
10
Where is Folate found?
green, leafy vegetables, dried beans, peas, sunflower seeds, citrus fruits, yeast, liver and kidney
Fortified Cereal Products
11
Where is Vitamin B12 found?
Animal products and fortified food
12
Where is Folate absorbed?
small intestine
13
Where is Vitamin B12 absorbed?
small intestine with acidic pH and intrinsic factor
14
How is folate taken up in the Reduced Folate Carrier?
High capacity
Low affinity
LV>folate>MTX
15
How is folate taken up in the Folate Receptor?
Low capacity
High affinity
Folate >>>MTX
16
Define Polygultamination
Addition of glutamine onto folate to keep folate inside of cells in order to increase affinity of TH4 for target enzymes
17
What two factors lead to differential sensitivity in cancer cells?
Over-expression of Folate Receptor in Choriocarcinoma
Better Polyglutamination
18
What are the leading contributors to folate deficiency?
Insufficient dietary intake
High demand (pregnancy)
Alcoholism
Intestinal disease (celiac sprue)
Inhibitors
19