6. Vit B12 and folate Flashcards
why do we need B12
- maintain function of brain and nervous system
- formation of blood cells
- involvde in metabolism of most cells
- key role in DNA synthesis/regulation
how is gastric acid important for B12 absorption
allows b12 to be released from food
can be accessible for absorption
what is haptocorrin
(type of transcobalamin) binds B12 to form haptocorrin-B12 complex
acts as carrier protein
= serves to protect it from degradation by stomach acid
where is intrinsic factor released from
gastric parietal cells
where does B12/IF complex move to
ileum
is IF recycled
no
constantly need to produce more
how would B12 get to target cell
is carried in circulation by transcobalamin
- lysosomal degradation of TC
- release of B12
vitamin B6 other name
pyridoxine
what does B6 do
convert succinyl coA and glycine into ALA (aminolevulinic acid)
(ALA then turns into haem)
what does B12 do in process of making haem
convert methymalonyl- coA into succinyl coA
what other metabolic process does B12 act as a cofactor for
converts homocysteine to methionine
how much B12 needed a day
1-3 micrograms
where is B12 sotred
liver
3-5mg stored
(takes a while to get deficient)
loss of B12
urine and faeces
desquamation of epithelial cells
(normal excretion)
vitamin B9
folate
how do we get folate
incapable of synthesizing it
so must come from diet
bakers yeast?
study doen in 30s
- giving bakers yeast= corrected anaemia in pregnant women
- wasnt known what exaclty it was
- but knew it was necassary for healthy blood cell production
what does be reduced to for it to be used
tetrahydrofolate
(the acitve form)
what does tetrahydrofolate get converted to
methyltetrahydrofolate
which is then used in nucleic acid synthesis
which precursors of DNA is folate responsible for
purine and pyrimidine precursors
how can veganism cause B12 def
no B12 in plants
what is pernicious anaemia
impaired absorption of B12, not because of a lack of b12, but a lack of functioning intrinsic factor
causes of folate deficiency
- poor dietry habits = chronic alcoholics or drugs can affect folate metabolism
- Crohns disease, or other diseases that impacts absorption in GI tract
- increased demand = e.g. MAINLY pregnancy, growth
- anticonvulsants (need to consider if pregnant woman taking them )
when does neural tube close
~ 28th day of pregnancy
nervous system develops
(because is so early, suggest supplements be taken before conception where possibile)
folate or B12 deficiency in early pregancy causes:
spina bifida ( neural tube defects) due to need for folate and B12 when cells rapidly proliferating
neurological complications from folate and B12 deficiency
preogressive demyleination of nerve cells
(POSSIBLY from increase in methylmalonyl- coA)
clinical features/symptoms of folate and B12 deficiency
- neuropathhy
- tingling in feet = difficulty in gait
- glossitis
what 2 haematological disorders do B12/folate deficiency cause
- megaloblastic anaemia (folate)
- pernicious anaemia (b12 def)
why are cells megaloblastic
low folate reduces dUMP to dTMP conversion
so DNA synthesis is delayed
= protein synthesis continues cuz RNA not affected as much = cell division delayed, but cell grows regardless
are megaloblasts fully fucntioning
no, not same amouont of O2 carried
MCV in megaloblastic anaemia
> 90fL
what is seen in blood film in meglaoblastic anaemia
- less cell divisions
- oval macrocytes
- increased lobe number in neutrophils
causes of pernicious anaemia
- autoimmune attack on gastric mucosa
- or genetic
how can we test if pernicious anaemia is autimmune
- antibody test
- antibodies against gastric parietal cells are found in serum in 85% of patients
what would you test for for pernicious anaemia
MCV increased
then test for methymalonyl- coA
(historically used Schilling method)
pernicious anaemia treatment
vitamin B12 intramuscular injection
hydroxycobalamin
how to treat meglaoblastic anaemia folate deficiency
oral dose of folic acid
what must be ruled out before treating with folate and why
vit b12 deficiency must be ruled out
- anaemia can alleviate but neurologic deficits will not
serum folate levels that suggest deficiency
<3micrograms /L
B12 levels that suggest deficiency
< 200 pg/mL
