EXAM #1: FOLATE & VITAMIN B12 METABOLSIM Flashcards Preview

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Flashcards in EXAM #1: FOLATE & VITAMIN B12 METABOLSIM Deck (42)
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1

List the major dietary sources of folate.

Spinach
Lettuce
Broccoli

****Think FOLATE i.e. FOLIAGE. Also, remember that folate is removed from vegetables by prolonged cooking/ boiling.*****

2

What structural feature distinguishes dietary folate from folate found in supplements?

- Dietary= polyglutamate
- Supplement= monoglutamate

3

What enzyme converts folate to tetrahydrofolate (THF)? What drug inhibits this enzyme?

- Diydrofolate reductase
- Methotrexate


*****Remember that THF and THF derivatives of THF are the active forms of THF in the body.*****

4

What is the most oxidized form of THF?

N10-formyl THF

5

What is the most reduced form?

N5-methyl THF

6

What is the one-carbon pool?

One carbon groups attached to THF that can be oxidized or reduced while bound to THF

7

Which reaction is the source of most of the carbon in the one-carbon pool?

Serine hydroxymethyltransferase reaction.

Serine + THF = Glycine + N5,N10 methylene-THF + H20

8

How is dietary folate absorbed in the intestine?

1) Hydrolysis of polyglutamate to monoglutamate
2) Monoglutamate form is absorbed
3) Reduction
4) Methylation

*****Product is N5-methyl THF, the most abundant form of folate in the circulation*****

9

How is folate released into the circulation?

Monoglutamate form of folate is eventually methylated to form "N5-methyl THF" that enters the circulation

10

What is the major form of THF in the circulation?

N5-methyl THF

11

How is folate taken up from the circulation?

Receptor-mediated endocytosis

- Receptors have high affinity for folate monoglutamate
- Receptors/N5-methyl THF are taken up
- Recycling of the receptor

12

What happens to folate inside the cell? Why is this modification important?

1) Conversion from monoglutamate to polyglutamate

*****Polyglutamate form keeps folate IN the cell i.e. prevents diffusion through the cell membrane*****

13

Which reaction requiring folate derivatives appears to be of greatest clinical importance?

Thymidylate synthase

- dUMP to dTMP, which is essential for DNA synthesis

14

What is the ultimate source of all vitamin B12?

Only synthesized by certain BACTERIA

****Note that B12 is also referred to as cyanocobalamin b/c of a cobalt group in the center--this is the form that is contained in supplements for vegans****

15

What are some important dietary sources?

- Liver
- Kidney
- Meat
- Dairy
- Shellfish

*****Though it is made by BACTERIA, B12 is stored in these organs*****

PLANTS DO NOT CONTAIN B12

16

Describe how vitamin B12 is liberated from food?

1) HCl and pepsin liberate B12 from food
2) B12 binds R-proteins
3) B12-R-proteins travel to the intestine

17

How is B12 absorbed in the intestine?

1) Pancreatic proteases remove R-proteins
2) B12 binds intrinsic factor
3) B12/IF undergoes receptor mediated endocytosis in the ILEUM

18

Describe how vitamin B12 is transported in the blood.

- Cells of the ileal mucosa make TRANSCOBALAMIN
- B12 is secreted into the blood as B12/transcobalamin

*****Note that most of the B12 in the blood is bound to HAPTACORRIN*****

19

How is B12 taken up by tissues?

Receptor mediated endocytosis of B12/transcobalamin

20

What are the metabolically active forms of vitamin B12?

Adenosylcobalamin
Methycobalamin

21

Describe how Part 1 and Part 2 of the Schilling test are performed.

Schilling test is a way of evaluating a patient's ability to absorb B12.

Part1=
- oral load of radioactive B12
- injection of non-radioactive B12
- 24 hour urine collection
- Radioactive excreted in urine, normal = 7%

Part2=
- oral radioactive B12
- oral purified IF
- same processing

22

What does an abnormal Part 1 but normal Part 2 tell you?

Pernicious anemia
- Not getting into the blood b/c of lack of IF
- Normal part 2 b/c of supplemented IF

23

How about abnormal Part 1 and Part 2?

NOT pernicious anemia b/c it was not fixed by IF administration

24

Describe the role of adenosylcobalamin in propionate metabolism. What does a deficiency in adenosylcobalamin result in?

methylmalonyl-CoA mutase in propionyl-CoA metabolism require ADENOSYLCOBALAMIN

Deficiency= methylmaloyl acidemia

25

Describe the role of methylcobalamin in homocysteine metabolism.

Methylcobalamin is required for Methionine synthase

26

What is meant by the ‘methyl trap hypothesis’?

- Methionine synthase converts N5, N10-mehtyl THF back to THF (requires methylcobalamin)
- Without B12, Folate becomes trapped in N5-methyl THF form

*****A FUNCTIONAL folate deficiency exists b/c this form cannot participate in the necessary biochemical reactions*****

27

What is megaloblastic anemia?

Anemia characterized by overgrowth of RBCs and RBC destruction

28

Why does deficiency of either folate or vitamin B12 result in a megaloblastic anemia?

- Vitamin B12 deficiency leads to functional folate deficiency (trapped as N5-methyl THF)
- Dietary insufficency may lead to actual folate deficiency

1) Thymidylate synthase is impaired dUMP-->dTTP
2) dUTP is incorporated into DNA instead
3) Cells GROW but CANNOT DIVIDE

****Eventually leads to DNA fragmentation and cell death and appears in rapidly dividing cells i.e. RBCs*****

29

What circumstances might increase folate needs?

1) Pregnancy
2) Lactation
3) Growth
4) Chronic hemolytic anemia

30

Under what circumstances may folate deficiency be seen in a patient?

1) Alcoholism
2) Old age
3) Poverty
4) Malabsorption syndrome