B12 Flashcards
4 Important aspects of vitamin B12:
- Absorption process is complex with R, IF, TCII
- Relation to folate: share a pathway
Homocysteine to methionine to SAM - Food sources – animal (microbiological) sources only
- Deficiency - irreversible neurological damage -
chemical name
cobalamin
natural B12 coenzyme form
cobalamin (unstable in supplements)
synthetic B12 coenzyme form
cyanocobalamin- supplements
2 coenzyme reactions
- cobalamin <-> methylcobalamin
enzyme: methionine synthase
function: methyl donor to make MET from HCY - propionyl CoA -> succinyl CoA
enzyme: methylmalonyl CoA mutase
function: 5’-deocyadenosylcobalamin coenzyme in above reaction
B12 stomach digestion
food based is protein bound so denature w HCl anddigest protein w pepsin
unbound: binds to protein R to prevent breakdown in stomach acid
R= haptocorrins in saliva and gastric juice
stomach parietal cells release IF (glycoprotein)
IF= intrinsic factor that binds B12 through intestine
B12 absorption in duodenum
pancreatic enzymes hydrolyze R
B12 released from R and binds IF
B12-IF complex travels to ileum
B12 absorption at ileum
cell receptors to absorb B12-IF complex, B12 absorbed by active process - endocytosis 50% efficient
when only B12, no IF, only passive absorption under 1%
once absorbed B12 transported in plasma attached to transcobalamin2 / holotranscobalamin
B12 enterohepatic circulation
B12 recycled in bile from liver storage
B12 binds IF and reabsorbed into ileum, treated like dietary
if no IF in body, body loses all stores of B12 quickly (months)
cobalamin/methylcobalamin function
enzyme: methionine synthase
HCY + methyl-THF -> MET +THF
lack of cobalamin = methyl trap!!
deficiency B12 same signs as folate def unless dietary folate excess (megaloblastic anemia, neural tube defects
heart disease, poor cognition, cancer)
5’-deocyadenosyl-B12 function
PropionylCoA + CO2 = succinyl CoA
methylmalonyl CoA mutase uses 2 subunits that require 5’deoxyadenosyl cobalamin
if B12 def, methylmalonic acid (MMA) builds up - abnormal metabolite
important diagnostic determinant if def in B12, MMa DOESNT CHANGE IN FOLATE DEF
symptoms unique to B12 def
pernicious anemia = megaloblastic anemia w nerve damage or neuropathy alone
this anemia bc of methyl trap and reduced ability to use folate in DNA synthesis
food sources of B12
B12 derived from microbial synthesis : meat, eggs, dairy
oysters and mackerel
bacteria in our large intestine can make B12 but we don’t absorb it there
B12 RDA
2.4mcg
absorption assumed 50%, loss of 1mcg
EAR set to maintain stores and account for availability
B12 UL
none
primary B12 def
lack of B12 in diet
vegan, high-income countries
secondary B12 def
possible when meeting RDA but:
- low stomach acid: can’t release B12 from food, supplements of fortified food okay
- pancreatic insufficiency: B12 not release from R, doesn’t bind IF so not well absorbed in ileum
- ileum resection: no receptor sites for absorption, need vitamin injection
- antibodies made against IF: secreted by stomach parietal cells (autoimmune in ppl over 50 yo) B12 absorbed passively only 1%, need mage doses
importance of liver stores of B12
excreted in bile then absorbed again (enterohepatic circulation)
adult can survive many years on low B12 intake if normal liver stores, unless body loses ability to reabsorb bile bc of no IF
if we can’t absorb B12 bc of low IF, we can’t reabsorb recycled B12, lose stores quickly
this explains why primary def in vegans can take years while secondary def can take only months in older adults w pernicious anemia
unique B12 test of status
low serum = low holotranscobalamin
high MMA
shared w folate B12 tests
high serum levels of HCY
unique test for folalte def
low serum folate
clinical and physical symptoms of B12 def
megaloblastic anemia: methyl trap
excess folate could mask B12, symptoms disappear when folate intake is high = reason for UL of folate
neuropathy: lose feeling in fingers, toes, hands, feet, eventually dementia
