30: Folate and vitamin B12 metabolism - Wilson Flashcards Preview

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Flashcards in 30: Folate and vitamin B12 metabolism - Wilson Deck (28):
1

sources of folate

green leafy vegetables (spinach, lettuce, broccoli)

water-soluble and readily removed by prolonged cooking

also organ meats (liver, kidney, etc)

2

functional form of folate

tetrahydrofolate THF

formed from folate by dihydrofolate reductase

3

what are the actions of dihydrofolate reductase?

converts folate to dihydrofolate and coverts dihydrofolate to THF

4

folate analog that inhibits dihydrofolate reductase

methotrexate

prevents generation of THF

antiproliferative effects

5

major source of one carbon groups

serine hydroxymethyltransferase

converts serine into glycine making a one-carbon

6

which form of folate is taken into the intestinal epithelial cell?

monoglutamate form

reduction and methylation occur in the cell to form N5methyl THF which is released into the blood

7

what is the majority of folate in your body?

N5 methyl THF (most reduced form)

8

method of folate uptake from blood

receptor mediated endocytosis

receptors have high affinity for folate monoglutamates

rapidly metabolized in the cell

9

converts dUMP to dTMP

thymidylate synthase

essential for DNA synthesis

10

methionine synthesis

THF form used:
folate form produced:

N5 methyl THF
THF

11

best dietary sources of vitB12

liver, kidney, other meats, dairy products, shellfish

plant foods do not supply vit B12

ONLY synthesized by certain bacteria

12

cyanocobalamin aka

vit B12

four cobalamins in human metabolism: cyanocobalamin, hydroxycobalamin, adenosylcobalamin*, methylcobalamin*

* biologically active forms

13

where is dietary B12 absorbed?

ileum - needs intrinsic factor

see slide 13

14

lack of ability to absorb vit B12 from ileum

pernicious anemia

autoimmune disease with gastric atrophy, no intrinsic factor produced

15

how is B12 taken from the blood?

receptor-mediated endocytosis with a transcobalamin recetors

16

B12 is secreted into blood as...

B12/transcobalamin complex

cells of ileal mucosa make TC

17

binding of B12 to TC required for uptake into cells, but most B12 in circulation is bound to ______

haptocorrin

this complex is taken up by liver (B12 secreted into bile, binds to haptocorrin again in bile, degraded in duodenum, binds intrinsic in ileum, etc)

18

describe the schilling test

Part 1: oral load of radioactive B12 and injection of non-radioactive B12. Normal individual excrete at least 7% of radioactivity within 24 hr.
Part 2: oral radioactive B12 and purified intrinsic factor.

abnormal P1 normal P2 = pernicious anemia

abnormal P1 and P2 = defect in B12 absorption independent of intrinsic factor

19

2 metabolic processes requiring vit B12

propionyl-coA metabolism (adenosylcobalamin)

homocysteine metabolism (methylcobalamin)

20

methyl trap hypothesis

folate trapped in N5methyl THF form --> functional folate deficiency

why? lack of b12 prevents sysnthesis of methylcobalamin, only methionin synthase can convert N5methyl THF back to THF

21

neurological consequences of vit B12 deficiency?

vit B12 results in demyelination

more likely failure of methionine synthase rxn, improve with methionine administration

22

functional v. actual folate deficiency

in either case: thymidine synthesis blocked (DNA synthesis blocked****) , purine synthesis also blocked

vit B12 deficiency leads to function folate deficiency with accumulation of N5methyl THF

dietary insufficiency may lead to actual
folate deficiency

23

___ incorporated into DNA instead of DTTP

dUTP

because of thymdiylate synthase

cells grow but can't divide --> DNA fragmentation and cell death. megaloblastic anemia in RBC too .

24

folate needs increased by

pregnancy
lactation
growth
chronic hemolytic anemia


a deficiency often seen in alcoholism, old age, poverty, celiac disease, malabsorption

25

deficient in B12 and folate?

probably alcoholic

26

vit B12 needs increased by

pregnancy
periods of growth

deficiency seen in:
strict vegans
pernicious anemia
celiac disease
gastric acid insufficiency
ileitis
fish tapeworm infestation
competing intestinal flora

27

acute megaloblastic anemia can be associated with

nitrous oxide anetsthesia

nitrous oxide destroys methylcobalamin**

28

classic B12 deficiency signs

pancytopenia
megaloblastic abnormalities in bone marrow
methylmalonic aciduria
hyperhomosyteinemia