Flashcards in 30: Folate and vitamin B12 metabolism - Wilson Deck (28):
sources of folate
green leafy vegetables (spinach, lettuce, broccoli)
water-soluble and readily removed by prolonged cooking
also organ meats (liver, kidney, etc)
functional form of folate
formed from folate by dihydrofolate reductase
what are the actions of dihydrofolate reductase?
converts folate to dihydrofolate and coverts dihydrofolate to THF
folate analog that inhibits dihydrofolate reductase
prevents generation of THF
major source of one carbon groups
converts serine into glycine making a one-carbon
which form of folate is taken into the intestinal epithelial cell?
reduction and methylation occur in the cell to form N5methyl THF which is released into the blood
what is the majority of folate in your body?
N5 methyl THF (most reduced form)
method of folate uptake from blood
receptor mediated endocytosis
receptors have high affinity for folate monoglutamates
rapidly metabolized in the cell
converts dUMP to dTMP
essential for DNA synthesis
THF form used:
folate form produced:
N5 methyl THF
best dietary sources of vitB12
liver, kidney, other meats, dairy products, shellfish
plant foods do not supply vit B12
ONLY synthesized by certain bacteria
four cobalamins in human metabolism: cyanocobalamin, hydroxycobalamin, adenosylcobalamin*, methylcobalamin*
* biologically active forms
where is dietary B12 absorbed?
ileum - needs intrinsic factor
see slide 13
lack of ability to absorb vit B12 from ileum
autoimmune disease with gastric atrophy, no intrinsic factor produced
how is B12 taken from the blood?
receptor-mediated endocytosis with a transcobalamin recetors
B12 is secreted into blood as...
cells of ileal mucosa make TC
binding of B12 to TC required for uptake into cells, but most B12 in circulation is bound to ______
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)
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
2 metabolic processes requiring vit B12
propionyl-coA metabolism (adenosylcobalamin)
homocysteine metabolism (methylcobalamin)
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
neurological consequences of vit B12 deficiency?
vit B12 results in demyelination
more likely failure of methionine synthase rxn, improve with methionine administration
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
___ incorporated into DNA instead of DTTP
because of thymdiylate synthase
cells grow but can't divide --> DNA fragmentation and cell death. megaloblastic anemia in RBC too .
folate needs increased by
chronic hemolytic anemia
a deficiency often seen in alcoholism, old age, poverty, celiac disease, malabsorption
deficient in B12 and folate?
vit B12 needs increased by
periods of growth
deficiency seen in:
gastric acid insufficiency
fish tapeworm infestation
competing intestinal flora
acute megaloblastic anemia can be associated with
nitrous oxide anetsthesia
nitrous oxide destroys methylcobalamin**