B12 and folate metabolism

Question 1

folate is typically found in what form?

Answer 1

polyglutamates

Question 2

what is the functional form of folate?

Answer 2

tetrahydrofolate (THF)

Question 3

what enzyme converts folate to THF?

Answer 3

dihydrofolate reductase

Question 4

what is the mechanism of action for the antineoplastic drug methotrexate?

Answer 4

folate analog that inhibits dihydrofolate reductase - prevents DNA synthesis (antiproliferative)

Question 5

what is the major reaction that produces 1 carbon groups?

Answer 5

conversion of serine to glycine

serine + THF = glycine + n5n10-methylene THF

Question 6

folate is absorbed in what form?

Answer 6

monoglutamate

Question 7

monoglutamate is converted to what form once inside the intestinal cells?

Answer 7

N5-methyl THF

Question 8

what is the most abundant form of folate in circulation?

Answer 8

N5-methyl THF

Question 9

folate is taken up by what process?

Answer 9

receptor mediated endocytosis

Question 10

how is folate retained within the intestinal cell?

Answer 10

converted to polyglutamate form

Question 11

why is methionine synthase important to folate metabolism?

Answer 11

only way to convert the most reduced form of folate to something more oxidized is with methionine synthase

Question 12

what is the function of thymidylate synthase?

Answer 12

1. converts dUMP to dTMP

2. essential for DNA synthesis

Question 13

what are the biologically active cobalamins?

Answer 13

adenosyl and methyl

Question 14

where does intrinsic factor bind B12?

Answer 14

duodenum

Question 15

where does B12 absorption occur?

Answer 15

ileum (intrinsic factor required)

Question 16

what is the cause of pernicious anemia?

Answer 16

inability to absorb B12 from ileum

Question 17

what is the role of transcobalamin?

Answer 17

1. made by cells of ileal mucosa
2. binds to B12
3. enters circulation as B12 / TC complex

Question 18

what is the role of haptocorrin?

Answer 18

binds B12 in circulation - uptake in liver

Question 19

what is required for methylmalonyl CoA mutase?

Answer 19

adenosylcobalamin

Question 20

how is proprionyl CoA metabolism affected by B12 deficiency?

Answer 20

1. conversion of methylmalonyl CoA to succinyl CoA inhibited
2. methylmalonyl CoA accumulates
3. hydrolysis yields methylmalonic acid
4. ORGANIC ACIDEMIA

Question 21

how is homocysteine metabolism affected by B12 deficiency?

Answer 21

1. conversion of homocysteine and N5-methyl THF to methionine and THF inhibited
2. folate trapped in N5-methyl THF form
3. functional folate deficiency - incorrect oxidation state
4. METHYL TRAP

Question 22

what is the neurological consequence of B12 deficiency?

Answer 22

demyelination

Question 23

a dietary B12 deficiency can lead to what condition?

Answer 23

actual folate deficiency

Question 24

what is the consequence of either a functional or actual folate deficiency?

Answer 24

1. thymidine synthase blocked (requires N5-methylene THF) - megaloblastic anemia
2. purine synthesis blocked
3. DNA synthesis prevented
4. neural tube defects