Lecture 2-Flolate Flashcards
Folate
What are key sources of folate in the diet?
Dark green leafy vegetables, orange juice, legumes, liver,
Folate is mediatory fortified into what ??
Bread
and cereals
What is the difference between folate and folic acid, and what is their relationship to each other?
Folate is methyltetrahydrofolate and differs from folic acid by a methyl group and 4 extra
carbons.
Folic acid is a pre vitamin - needs to be reduced to active form of folate = Tetrahydrofolate
They
have different carriers to cross cell walls and carry in blood.
What are the three main functions of folate in the body? For each, list at least three key
components of the relevant pathway
DNA synthesis
Purines
DNA methylation
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 structure can we not make
- Humans can not make the middle bit
- We can also not combine all three so this is why it is an essential nutrient we get from our diet
what is folic acid
being added when the food is fortified
what is food folate
naturally present in food
where is folic acid usually found
supplements and food fortification
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
which one of food folate of Folic acid either a polyglutatmate or monoglutamate
Food folate =polyglutamate
Folic acid = monoglutamate
absorption and cell retention order
Gut lumen
Enterocyte
Blood
Cell
when are polyglutamates 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
what is DHFR (dihydrofolate reductase) do
add on hydrogens (reduction reaction) to get folate to the active form
add on hydrogens (reduction reaction) to get folate to the active form
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
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
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
Q
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