Folate Metabolism

Question 1

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

Answer 1

Green leafy vegetables

Cooking

Question 2

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

Answer 2

Polyglutamates

Tetrahydrofolate is the functional form

Question 3

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

Answer 3

Convert methylmalonyl-CoA to succinyl-CoA

Homocysteine to Methionine

Question 4

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

Answer 4

Dihydrofolate reductase

Methotrexate can inhibit production of THF, limiting cell growth

Question 5

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

Answer 5

Methyl carrier
Reduced = N5
Oxidized = N10

Question 6

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

Answer 6

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

Question 7

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?

Answer 7

Enterocytes hydrolyze poly to mono, then transport into circulation

Question 8

How is THF absorbed by cells in the body?

Answer 8

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

Question 9

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

Answer 9

N5-THF = circulation

Polyglutamase in the cells

Question 10

Why is THF polyglutaminated once inside the cell?

Answer 10

Helps keep the molecule within the cell

Question 11

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?

Answer 11

Methionine synthesis

B12 needed

Question 12

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

Answer 12

THF to N5, N10

Question 13

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

Answer 13

N5 THF to THF

Question 14

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

Answer 14

N5, N10 to Dihydrofolate

Question 15

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

Answer 15

N10-formyl THF to THF

Question 16

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

Answer 16

THF to N5-formino THF

Question 17

What does thymidylate synthease do? Why is this important?

Answer 17

Converts dUMP to dTMP

Essential for DNA synthesis

Question 18

What is the ultimate source of all B12?

Answer 18

Bacteria

Question 19

Do plants supply B12?

Answer 19

No, unless they have the bacteria that produce it

Question 20

What are the metabolically active forms of B12?

Answer 20

Adenosylcobalamin

Methylcobalamin

Question 21

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

Answer 21

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

Question 22

What cells in the stomach produce intrinsic factor?

Answer 22

Parietal cells

Question 23

Where is B12/intrinsic factor complex absorbed?

Answer 23

In the Ileum

Question 24

What is the transport protein for B12?

Answer 24

Transcobalamin (haptocorin)

Question 25

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

Answer 25

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

Question 26

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

Answer 26

Large quantities force it into cells

Question 27

What cells in the body form transcobalamin?

Answer 27

Ileal mucosa

Question 28

What are haptocorrins?

Answer 28

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

Question 29

What happens to haptocorrins when they enter the liver?

Answer 29

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

Question 30

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

Answer 30

- Oral load of radioactive B12 - Inject non-radioactive B12 - Screen urine for B12. Normal >7% Failure = inability to absorb B12

Question 31

What happens in part 2 of the Schilling test?

Answer 31

- Radioactive B12 administered orally w/ intrinsic factor | - IM injection of non-radioactive B12

Question 32

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

Answer 32

Intrinsic factor deficiency

Question 33

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

Answer 33

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

Question 34

Adenosylcobalamin is need for what reaction?

Answer 34

Converting L-methylmalonyl-CoA to succinyl-CoA

Question 35

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

Answer 35

``` AA (carboxylase) D-methylmalonyl-CoA (racemase) L-methylmalonyl CoA (mutase) Succinyl CoA ```

Question 36

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

Answer 36

Threonine Methionine Valine Isoleucine

Question 37

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

Answer 37

L-Methylmalonyl CoA

Question 38

What is the reaction that requires methylcobalamin?

Answer 38

Homocystiene to methionine +THF

Question 39

What is the folate trap?

Answer 39

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.

Question 40

What causes the demyelination seen with a B12 deficiency?

Answer 40

failure of methionine synthase reaction, and lack of SAM

Question 41

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

Answer 41

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

Question 42

How does megaloblastic anemia result from the loss of THF?

Answer 42

Purine synthesis is halted in the thymidylate synthase reaction

Question 43

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

Answer 43

dUMP to dTMP | N5, N10-methylene-THF

Question 44

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

Answer 44

Diphyllobothrium latum Fish tapeworm

Question 45

What is the anasthetic that destroys methylcobalamin?

Answer 45

NO2

Question 46

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

Answer 46

PPIs