1 Tetrahydrofolate Flashcards
(29 cards)
Three active structures of tetrahydrofolate
pteridine ring (site of redox) PABA (sulfa target) Polyglut tail (cleaved at GI)
Enzyme that oxidizes or reduces FH4
Dihydrofolate reductase
Crohns disease, alcohol, celiac disease does what to folate?
inhibit absorption at the intestinal mucosa
where can one carbon groups attach to FH4 and what does it mean?
N5 if most reduced N10 if most oxidized, most reduced form is a committed rxn
where does the one carbon for FH4 redox come from?
serine, glycine, histidine, tryptophan
what is the important dietary aspect about the serine one carbon pool
serine can be made from a glycolysis intermediate so can be made from dietary carbs
what is folate critical most importantly used in?
purine synthesis thus cell division
<p>
| How is dUMP made into dTMP</p>
<p>
| thymidylate synthase enzyme which uses a N5,10 methelene-FH4.... this results in FH2 and dTMP</p>
What does 5-FU target and what is it
5-FU blocks thymidylate synthase and is anti cancer chemo drug
how is FH4 regenerated from FH2
dihydrofolate reductase enzyme which uses up a NADPH
what does methotrexate target and what is it?
methotrexate targets dihydrofolate reductase and is anti cancer chemo drug
why do vegans have problems with b12 def?
B12 high in animal protein
what is the most important binder for b12 absorption?
intrinsic factor from the parietal cells, r-binders (haptocorrins) initially though
what are the two major functions of b12?
homocysteine to methionine (also uses folate) and methylmalonyl-CoA to succinyl CoA
what can def of intrinsic factor cause?
pernicious anemia
what does b12 bind w/ in the blood?
trancobalamin II
how does b12 distribute?
half to liver, half to other
why is b12 def rare?
years worth stored in liver
what is the schillings test?
4 steps to finding out if the cause of b12 def is form: malnutrition, malabsorption, intrinsic factor, bacterial, pancreatitis
how does folate relate to b12 which relate to methionine which relates to SAM?
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
what is betaine?
it is a oxidized choline which in the liver can xvert homocysteine to methionine like B12 but is only a minor path
what deficiencies can cause homocyteinemia?
def in b12 primarily and folate and PLP secondarily
Why doesn’t homocyteine simply convert to cysteine in homocysteinemia?
cysteine feedbacks so the shunt is inactivated with high homoocyteine
why is folate supplementation required for pregnancy?
folate def = neural tube defects
