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Hematology > Folate Metabolism > Flashcards

Folate Metabolism Flashcards

1
Q

What are the sources of Folate? What process takes out the folate form these food sources?

A

Green leafy vegetables

Cooking

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2
Q

What is the usual form of folate? What is the functional form of folate in the body?

A

Polyglutamates

Tetrahydrofolate is the functional form

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3
Q

What are the two major chemical pathways in the body that require THF?

A

Convert methylmalonyl-CoA to succinyl-CoA

Homocysteine to Methionine

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4
Q

What is the enzyme that converts folate to THF? Why is this an important drug target? What is the drug that inhibits it?

A

Dihydrofolate reductase

Methotrexate can inhibit production of THF, limiting cell growth

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5
Q

What is the function of THF? What is the most reduced form, and what is the most oxidized form?

A

Methyl carrier
Reduced = N5
Oxidized = N10

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6
Q

What is the reaction that is the major source of one carbon groups?

A

S +THF = G + (N5, N10-THF)

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7
Q

THF is found in foods mostly in a polyglutamate form, but it is found in the circulation in a monoglutamate form. What is the mechanism behind this?

A

Enterocytes hydrolyze poly to mono, then transport into circulation

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8
Q

How is THF absorbed by cells in the body?

A

Receptors take in N5-methyl-THF, then converted to polyglutamate form

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9
Q

What is the most abundant form of THF in the circulation? Inside cells?

A

N5-THF = circulation

Polyglutamase in the cells

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10
Q

Why is THF polyglutaminated once inside the cell?

A

Helps keep the molecule within the cell

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11
Q

What is the only reaction in the body that can convert N5-methyl-THF to THF? What is/are the vitamin(s) that is/are needed for this reaction to take place?

A

Methionine synthesis

B12 needed

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12
Q

What is the THF form used, and what is the form that is produced for: the S to G reaction?

A

THF to N5, N10

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13
Q

What is the THF form used, and what is the form that is produced for: methionine synthesis

A

N5 THF to THF

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14
Q

What is the THF form used, and what is the form that is produced for:thymidylate synthesis?

A

N5, N10 to Dihydrofolate

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15
Q

What is the THF form used, and what is the form that is produced for: purine synthesis?

A

N10-formyl THF to THF

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16
Q

What is the THF form used, and what is the form that is produced for: histidine catabolism?

A

THF to N5-formino THF

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17
Q

What does thymidylate synthease do? Why is this important?

A

Converts dUMP to dTMP

Essential for DNA synthesis

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18
Q

What is the ultimate source of all B12?

A

Bacteria

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19
Q

Do plants supply B12?

A

No, unless they have the bacteria that produce it

20
Q

What are the metabolically active forms of B12?

A

Adenosylcobalamin

Methylcobalamin

21
Q

What are the proteins in the stomach that bind free B12? What happens to the B12/protein complex when it enters the duodenum?

A

R proteins, which are degraded by pancreatic proteases, and intrinsic factor binds B12

22
Q

What cells in the stomach produce intrinsic factor?

A

Parietal cells

23
Q

Where is B12/intrinsic factor complex absorbed?

A

In the Ileum

24
Q

What is the transport protein for B12?

A

Transcobalamin (haptocorin)

25
Q

What is the cause of pernicious anemia (if not a dietary cause)?

A

Autoimmune attack against acid and pepsin secreting portion of the gastric mucosa

26
Q

B12 can be taken up in the absence of intrinsic factor. How?

A

Large quantities force it into cells

27
Q

What cells in the body form transcobalamin?

A

Ileal mucosa

28
Q

What are haptocorrins?

A

Proteins in the circulation that bind B12, and allow for hepatocytes to take up B12

29
Q

What happens to haptocorrins when they enter the liver?

A

Broken down, with B12 secreted into bile salts, to repeat the same process

30
Q

What happens in part 1 of the Schilling test? Failing this part of the test indicates what?

A
  • Oral load of radioactive B12
  • Inject non-radioactive B12
  • Screen urine for B12. Normal >7%

Failure = inability to absorb B12

31
Q

What happens in part 2 of the Schilling test?

A
  • Radioactive B12 administered orally w/ intrinsic factor

- IM injection of non-radioactive B12

32
Q

Abnormal part 1 of the schilling test, but a normal part 2, indicates what?

A

Intrinsic factor deficiency

33
Q

If both parts of the schilling test are abnormal, what does this indicate?

A

defective B12 absorption d/t other causes besides intrinsic factor deficiency

34
Q

Adenosylcobalamin is need for what reaction?

A

Converting L-methylmalonyl-CoA to succinyl-CoA

35
Q

What are the steps of taking AAs to succinyl CoA? (draw the pathway if needed)

A 
AA
(carboxylase)
D-methylmalonyl-CoA
(racemase)
L-methylmalonyl CoA
(mutase)
Succinyl CoA
36
Q

Which 5 amino acids can be converted into Succinyl-CoA?

A

Threonine
Methionine
Valine
Isoleucine

37
Q

A lack of adenosyl cobalamin will result in the accumulation of what metabolite in the blood/urine?

A

L-Methylmalonyl CoA

38
Q

What is the reaction that requires methylcobalamin?

A

Homocystiene to methionine +THF

39
Q

What is the folate trap?

A

since N5 THF is the most common type, but THF is needed, and B12 needed to do the conversion, a lack of B12 will result in the useless N5THF only.

40
Q

What causes the demyelination seen with a B12 deficiency?

A

failure of methionine synthase reaction, and lack of SAM

41
Q

Why is it, that if you lack B12, you also have a functional folate deficiency?

A

THF is stuck in the N5-THF form, since the methionine reaction cannot take place

42
Q

How does megaloblastic anemia result from the loss of THF?

A

Purine synthesis is halted in the thymidylate synthase reaction

43
Q

Thymidylate synthase converts what to what? What vitamine is needed?

A

dUMP to dTMP

N5, N10-methylene-THF

44
Q

What is the parasite that loves B12? What animal does this parasite come from?

A

Diphyllobothrium latum

Fish tapeworm

45
Q

What is the anasthetic that destroys methylcobalamin?

A

NO2

46
Q

What is the drug type that should be supplemented with B12?

A

PPIs

Hematology (32 decks)

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