Nutrition Lecture 2: Folate Flashcards
What are rich food sources of folate?
Green leafy vegetables, orange juice, lentils, beans, fortified bread and cereals, liver - 1 cup spinach = 40% RDI
How many parts is the basic structure of folate?
3 parts
What are the 3 parts of the folate structure?
- Double ringed pteridine structure
- P-aminobenzoic acid (PABA)
- A glutamate
Why is folate an essential nutrient?
Humans cannot make p-aminobenzoic acid nor can we join together these three molecules. Therefore it is essential to get folate from the diet, an essential nutrient, a vitamin
What is the difference between folic acid and folate?
Folic Acid = added when there is a fortification
Food Folate = naturally present in food
How do the structures differ between folic acid and food folate?
There is a methyl group on the food folate, not on the folic acid.
There are 4 hydrogens added onto the food folate.
What is the chemical name for food folate?
MTHF “methyltetrahyrdofolate”
Where is folic acid found?
In supplements and food fortification
Why do we use folic acid instead of food folate for fortification?
Folic acid is folate in its fully oxidized form, which means it is quite stable
Do food folate and folic acid have the same carriers?
No they have different carriers to cross cell walls
What does it mean that folic acid is a pre-vitamin?
It needs to be reduced to its active form of folate
What is the active form of folate?
THF - tetrahydrofolate
What is GCP II?
Removes extra glutamates on dietary polyglutamates (food folate) so they can transported into cells in mono form
Where does GCP II happen?
In the gut lumen
What is RFC?
Reduced folate carrier
What is FR?
Folate receptor
What is the role of RFC?
Transports what was originally food folate through and into the cell - now in its mono form
What is the role of FR?
transports folic acid through and into the cell
What is FPGS?
Folylpolyglutamate synthase
What is the role of FPGS?
FPGS polyglutamates both forms of folate to keep them in the cells - no longer in mono form
What is the structure of THF?
Hydrogens have been added from folic acid. THF has a methyl group removed from food folate
How is folate involved in our genetic material?
Folate is essential for DNA synthesis, production of purines and DNA methylation
How does the process of folate producing a thymine work?
When there is sufficient folate, dUMP is converted to dTMP and its thymine is incorporated into DNA
How is dUMP converted to dTMP?
DUMP binds methyl group from 5,10-MTHF to convert it to dTMP
What enzyme transfers the methyl group from 5,10-MTHF to dTMP?
TS - thymidylate synthase
What happens to DNA synthesis when there is insufficient folate?
dUMP is not converted to dTMP and uracil is misincorporated into DNA - uracil is incorperated instead of thymine
What nucleotide bases are formed from THF?
Purines
What are purines?
Adenine and Guanine
What are the roles of Adenine and Guanine?
- Nucleotide bases in DNA and RNA
- Part of AMP and GMP
What are AMP and GMP?
Activators that are converted into ATP and GTP to use as energy currencies
How is folate involved in DNA methylation?
Folate provides the methyl group for DNA methylation
What is DNA methylation used for?
Epigenetic modification
What is epigenetic modification?
A critical process in control of gene expression and stabilisation of the genome
What are the three main functions of folate?
- DNA synthesis
- Purines
- DNA methylation
When is homocysteine formed?
When the amino acid methionine is metabolised to cysteine
What is hyperhomocysteinemia associated with?
Increased risk of CVD and thrombosis
What is hyperhomocysteinemia?
too high concentration of cysteine in the blood
What are the four possible fates of homocysteine?
- Converted back to SAH
- Remethylated to form methionine
- Degradation, reduced into cystathionine
- If levels are too high will be released into blood
What happens is there is not enough folic acid?
You won’t be able to form THF and eventually a build up of homocysteine
What are symptoms of folate deficiency?
Tiredness, breathlessness = megaloblastic anaemia
What is megaloblastic anaemia?
very large red blood cells and a decrease in the number of those cells
What does folic acid reduce the risk of?
NTD - neural tube defects
What are the two main types of NTD?
- Spina bifida
- Anencephaly
What percent reductions in NTD’s in pregnancies with folic acid supplementation?
85% drop
What are the risks of high folic acid intake?
May obscure B12 deficiency, could delay diagnosis of neurological damage
Is there a risk of high food folate intake?
No risk
What is the upper limit for folic acid?
1000ug/day (adults)
What is the EAR for folate?
320ug/day
What is the RDI for folate?
400ug/day
What is the folate RDI for pregnant women?
600ug/day, if they are at risk for NTD this increases
