Lecture 2 - Folate Flashcards
what is vitamin is folate
B9
what are food sources of folate
- green leafy vegetables
- orange juice
- peanuts
- legumes and beans
- bread (mandatory fortified)
- range of breakfast cereals (fortified)
- liver
why is liver such an important source of folate
mammals store 50% of their folate in their liver, so consuming liver from animals is a useful source
what part of the folate molecule can humans not manufacture and what does this mean
the middle part
so therefore folate is essential in the diet
what is folic acid
being added when the food is fortified
what is food folate
naturally present in food
how is food folate chemical different to folic acid
methyl group is on food folate that isn’t on folic acid
where is folic acid usually found
supplements and food fortification
what is the name of the form of most food folate
methyltetrahydrofolate
what is meant by folic acid is a “pre vitamin”
needs to be reduced to active form of folate
what is the active form of folate
tetrahydrofolate
folic acid is in what form and why does this mean it is good to be used in fortification
fully oxidised form, it is quite stable and that is why it is used in fortification
is food folate polyglutamate or monoglutamate
polyglutamate
is folic acid polyglutamate or monoglutamate
monoglutamate
when are polyglutamates removed in absorption of folate
when it has entered the enterocyte
what helps more food folate into the cell
reduced folate carrier
what helps move folic acid into the cell
folate receptor
once both forms of folate are in the cell, what happens to keep them in the cell
both forms are polyglutamated
what is DHFR (dihydrofolate reductase) do
add on hydrogens (reduction reaction) to get folate to the active form
if converting from folic acid to the active form what has changed
hydrogens have been added
if converting from food folate to the active form what has changed
there has been removal of methyl group by enzymes
what are functions of folate
DNA synthesis, DNA methylation, purines
how is folate involved in DNA synthesis
when there is sufficient folate, dUMP is converted to dTMP and its thymine (one of the four nucleotide bases) is incorporated into DNA
what happens to DNA synthesis when there is insufficient folate
dUMP is not converted to dTMP, and uracil is misincorperated into DNA
purines are what nucleotide bases
A and G bases for nucleotides
purines are also what
part of AMP and GMP, which are converted to ATP and GTP to use as energy currencies
what does folate provide for DNA methylation and what is this used for
a methyl group which is used for epigenetic modification
what is epigenetic modification
a critical process in control of gene expression and stabilisation of the genome
how is folate linked to DNA methylation
- tetrahydrofolate has a methyl group added to it
- this gets converted to 5-methyltetrahydrofolate
- then conversion to methionine, then to SAM
- then number of steps to DNA methylation
when is homocysteine formed
when the amino acid methionine is metabolised to cysteine
what are the four possible fates of homocysteine
- reform s-adenosyl homocysteine (SAH)
- remethylation to form methionine
- degradation through transulfuration pathway
- leaks out of cell if intracellular concentration too high
hyperhomocysteinemia is associated with increased risk of what
increased risk of CVD and thrombosis
if there is not enough folic acid in the diet not enough what will be formed
not enough THF will be formed from folic acid
if there is not enough 5-methyl THF then not enough what will be formed
not enough THF will be formed
lacking 5-methyl THF means what for production of methionine
means you will not to be able to add on the methyl group to homocysteine to form methionine (stable compound)
what is the stable compound that homocysteine is converted to
methionine
if you are unable to form methionine because you are lacking in 5-methyl THF what will this mean
means you will have an increase in the homocysteine concentration and an increase in the SAH molecule as well
why will homocysteine levels stay elevated if there is damage to the 5-methyl THF
you can not pump all of the homocysteine into SAH so will be left with higher levels of homocysteine
a case study on 22 year old female student on a largely CHO diet but not vegetarian reported symptoms of tiredness and breathlessness on minimal exertion, what did she have and what was the reason
megaloblastic anaemia due to folate deficiency
what are megaloblasts
really big compared to normal red blood cells, they are the immature form
how is folate linked to meglaloblastic anaemia
you need folate to form the nucleotide bases to form DNA
- without enough folate proper cell devision does not occur and there for formation of the red blood cell does not happen properly and it enters the circulation still containing its nucleus
what is another effect of folate deficiency
neural tube defects
what are the complications that come with neural tube defects
below the defect you will get abnormal nerve conduction, so you will have issues with motor and sensory control / function
what are the two main types of neural tube defects and what are they
spina bifida (lesion on the spine)
anencephaly (not compatible with life)
approximately how many cases of neural tube defects are there in NZ each year
approx 64
what part of New Zealand has higher rates of neural tube defects
the north island
what is the folate toxicity rates from naturally occurring folate in foods
no risk
high folic acid intake may lead to
- obscure vitamin B12 deficiency
- leading to delay in diagnosis of neurological damage
what is the upper limit of folate for fortified foods or supplements
1,000μg/day (adults)
what is ministry of health recommendation of RDI and EAR of folate for adult men and women
EAR : 320μg/day
RDI : 400μg/day
what is ministry of health recommendation of RDI and EAR of folate during pregnancy
RDI : 600μg/day
why is it important to have fortification of food with folate (pregnancy)
~53% of pregnancies are unplanned so they will not be taking a supplement which is why food sources need to be fortified
