1 Tetrahydrofolate

Question 1

Three active structures of tetrahydrofolate

Answer 1

pteridine ring (site of redox) PABA (sulfa target) Polyglut tail (cleaved at GI)

Question 2

Enzyme that oxidizes or reduces FH4

Answer 2

Dihydrofolate reductase

Question 3

Crohns disease, alcohol, celiac disease does what to folate?

Answer 3

inhibit absorption at the intestinal mucosa

Question 4

where can one carbon groups attach to FH4 and what does it mean?

Answer 4

N5 if most reduced N10 if most oxidized, most reduced form is a committed rxn

Question 5

where does the one carbon for FH4 redox come from?

Answer 5

serine, glycine, histidine, tryptophan

Question 6

what is the important dietary aspect about the serine one carbon pool

Answer 6

serine can be made from a glycolysis intermediate so can be made from dietary carbs

Question 7

what is folate critical most importantly used in?

Answer 7

purine synthesis thus cell division

Question 8

<p>

| How is dUMP made into dTMP</p>

Answer 8

<p>

| thymidylate synthase enzyme which uses a N5,10 methelene-FH4.... this results in FH2 and dTMP</p>

Question 9

What does 5-FU target and what is it

Answer 9

5-FU blocks thymidylate synthase and is anti cancer chemo drug

Question 10

how is FH4 regenerated from FH2

Answer 10

dihydrofolate reductase enzyme which uses up a NADPH

Question 11

what does methotrexate target and what is it?

Answer 11

methotrexate targets dihydrofolate reductase and is anti cancer chemo drug

Question 12

why do vegans have problems with b12 def?

Answer 12

B12 high in animal protein

Question 13

what is the most important binder for b12 absorption?

Answer 13

intrinsic factor from the parietal cells, r-binders (haptocorrins) initially though

Question 14

what are the two major functions of b12?

Answer 14

homocysteine to methionine (also uses folate) and methylmalonyl-CoA to succinyl CoA

Question 15

what can def of intrinsic factor cause?

Answer 15

pernicious anemia

Question 16

what does b12 bind w/ in the blood?

Answer 16

trancobalamin II

Question 17

how does b12 distribute?

Answer 17

half to liver, half to other

Question 18

why is b12 def rare?

Answer 18

years worth stored in liver

Question 19

what is the schillings test?

Answer 19

4 steps to finding out if the cause of b12 def is form: malnutrition, malabsorption, intrinsic factor, bacterial, pancreatitis

Question 20

how does folate relate to b12 which relate to methionine which relates to SAM?

Answer 20

folate can add one carbon group to carbon or sulfur atoms so it donates to b12 which donates the carbon to homocysteine which makes methionine which donate one carbon to SAH to make SAM which can donate the carbon to a nitrogen or oxygen

Question 21

what is betaine?

Answer 21

it is a oxidized choline which in the liver can xvert homocysteine to methionine like B12 but is only a minor path

Question 22

what deficiencies can cause homocyteinemia?

Answer 22

def in b12 primarily and folate and PLP secondarily

Question 23

Why doesn’t homocyteine simply convert to cysteine in homocysteinemia?

Answer 23

cysteine feedbacks so the shunt is inactivated with high homoocyteine

Question 24

why is folate supplementation required for pregnancy?

Answer 24

folate def = neural tube defects

Question 25

what is a cooking consideration for vegetables for folate consumption?

Answer 25

boiling will destroy folate

Question 26

what is and causes megaloblastic anemia?

Answer 26

limited DNA synthesis causes abnormally large RBCs to be released. Due to decreased T and purines, results from b12 and or folate deficiency, req schilling test or precursor measurement for differentiation

Question 27

why can age cause b12 def?

Answer 27

lowered release of pepsin can limit b12 release from proteins -> treat with iv b12

Question 28

how does sulfa drugs work on bacteria?

Answer 28

on the PABA ring of FH4

Question 29

what precursors would accumulate in what deficiencies folate and B12?

Answer 29

b12 deficiency -> homocysteine and methylmalonyl CoA build up

Folate only deficiency -> Homocysteine build up only