Folate, B12, and Inhibitors - Fitz

Question 1

What is the first symptom of a vitamin B12 or Folate deficiency?

Answer 1

Megaloblastic Anemia

Question 2

What cell processes is folate a carbon donor to?

Answer 2

Thymidylate Synthesis
Purine Synthesis
Amino Acid Metabolism

Question 3

Vitamin B12 is a cofactor in the generation of what?

Answer 3

Tetrahydrofolate (from methylTH4)

Methylmalonyl CoA to Succinyl CoA

Question 4

What is one cause of primary resistance in low doses of folate inhibitors?

Answer 4

Reduced expression of the Reduced Folate Carrier (RFC)

Question 5

How does Leucovorin function?

Answer 5

Allows normal cells with functional RFC to overcome the drug induced inhibition of dihydrofolate reductase

Question 6

How does Trimethoprim-Sulfamethoxazole work?

Answer 6

Trimethoprim = folic acid inhibitor
Sulfamethoxazole = blocks dihydropteroate synthetase
=>Blocks Folate Synthesis pathway via bacterial dihydrofolate reductase

Question 7

What laboratory finding is diagnostic of a Vitamin B12 Deficiency?

Answer 7

Homocysteine (converted to methionine via B12 catalysis)

Question 8

How is leucovorin used in rescue therapy?

Answer 8

Replaces folate by being converted to TH4

Question 9

What are the naturally occuring forms of Vitamin B12?

Answer 9

Adenosylcobalamin

Methylcobalamin

Question 10

Where is Folate found?

Answer 10

green, leafy vegetables, dried beans, peas, sunflower seeds, citrus fruits, yeast, liver and kidney
Fortified Cereal Products

Question 11

Where is Vitamin B12 found?

Answer 11

Animal products and fortified food

Question 12

Where is Folate absorbed?

Answer 12

small intestine

Question 13

Where is Vitamin B12 absorbed?

Answer 13

small intestine with acidic pH and intrinsic factor

Question 14

How is folate taken up in the Reduced Folate Carrier?

Answer 14

High capacity
Low affinity
LV>folate>MTX

Question 15

How is folate taken up in the Folate Receptor?

Answer 15

Low capacity
High affinity
Folate&raquo_space;>MTX

Question 16

Define Polygultamination

Answer 16

Addition of glutamine onto folate to keep folate inside of cells in order to increase affinity of TH4 for target enzymes

Question 17

What two factors lead to differential sensitivity in cancer cells?

Answer 17

Over-expression of Folate Receptor in Choriocarcinoma

Better Polyglutamination

Question 18

What are the leading contributors to folate deficiency?

Answer 18

Insufficient dietary intake
High demand (pregnancy)
Alcoholism
Intestinal disease (celiac sprue)
Inhibitors

Question 19

What is the leading cause of Vitamin B12 deficiency?

Answer 19

Malabsorption due to Intrinsic Factor deficiency –> will cause folate deficiency by preventing access to stored TH4