B12 and folate metabolism Flashcards Preview

Year 2 Hematology > B12 and folate metabolism > Flashcards

Flashcards in B12 and folate metabolism Deck (24)
1

folate is typically found in what form?

polyglutamates

2

what is the functional form of folate?

tetrahydrofolate (THF)

3

what enzyme converts folate to THF?

dihydrofolate reductase

4

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

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

5

what is the major reaction that produces 1 carbon groups?

conversion of serine to glycine

serine + THF = glycine + n5n10-methylene THF

6

folate is absorbed in what form?

monoglutamate

7

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

N5-methyl THF

8

what is the most abundant form of folate in circulation?

N5-methyl THF

9

folate is taken up by what process?

receptor mediated endocytosis

10

how is folate retained within the intestinal cell?

converted to polyglutamate form

11

why is methionine synthase important to folate metabolism?

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

12

what is the function of thymidylate synthase?

1. converts dUMP to dTMP
2. essential for DNA synthesis

13

what are the biologically active cobalamins?

adenosyl and methyl

14

where does intrinsic factor bind B12?

duodenum

15

where does B12 absorption occur?

ileum (intrinsic factor required)

16

what is the cause of pernicious anemia?

inability to absorb B12 from ileum

17

what is the role of transcobalamin?

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

18

what is the role of haptocorrin?

binds B12 in circulation - uptake in liver

19

what is required for methylmalonyl CoA mutase?

adenosylcobalamin

20

how is proprionyl CoA metabolism affected by B12 deficiency?

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

21

how is homocysteine metabolism affected by B12 deficiency?

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

22

what is the neurological consequence of B12 deficiency?

demyelination

23

a dietary B12 deficiency can lead to what condition?

actual folate deficiency

24

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

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