Folate Flashcards
What is the difference between folate and folic acid?
Folate = naturally occurring in food; many chemical forms
Food sources: leafy greens & peas; legumes
Folic acid = synthetic form found in supplements and fortified foods
Folic acid is much more bioavailable than the folate that naturally occurs in foods
How can folic acid mask a vitamin B12 deficiency?
Both folate and B12 deficiency can result in megaloblastic anemia
Elevated levels of homocysteine levels are seen in folate and vitamin B12 deficiency (further differentiation is needed to determine which deficiency is it (if not both).
Very high-dose folic acid supplementation (such as 5,000 ug/day) can mask a B12 deficiency (specifically, signs of nerve damage)
The symptoms of a B12 deficiency can be masked by folate supplementation and therefore progressing the possible neurological damage of a B12 deficiency without symptoms to indicate this damage is occurring.
What are the main functions of folate?
required for DNA synthesis
supports cell growth and repair (methylation)
helps prevent neural tube defects
What is the daily recommendation for folate?
Adults: 400 ug DFE
Pregnant women: 600 ug DFE
DFE = unit of measurement that accounts for differences in the absorption of naturally occurring food folate and synthetic folic acid
What are good dietary sources of folate (B9)?
Legumes: beans, peas, lentils
Green leafy vegetables: kale, spinach
Fortified foods & supplements: enriched bread, fortified cereals, etc.
Describe the folate cycle.
- folate transports dietary folate into the cell
- folate –> dihydrofolate (DHF)
- DHF –> tetrahydrofolate (THF) by dihydrofolate reductase (DHFR) (enzyme)
- THF –> 5,10-methylene THF, the substrate of 5,10-methyleneTHF reductase (MTHFR)
- MTHFR –> 5-methylTHF
- 5-methylTHF can be recycled by methionine synthase/methionine synthase reductase (MTR/MTRR) to THF and methionine
- Alternatively, 5-methylTHF can be used to synthesize purine
- methionine can be used in the methionine cycle to product S-adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH), and homocysteine
Dietary folate dihydrofolate (DHF)
DHF tetrahydrofolate (THF) (converted via dihydrofolate reductase - DHFR)
THF 5,10-methylene THF
5,10-methylene THF 5-methyl THF (converted via methylenetetrahydrofolate - MTHFR)
5-methyl THF can be recycled into methionine and THF via methionine synthase & B12
Where do the folate and B12 pathways overlap?
2 pathways to metabolize homocysteine
- methionine synthase - methionine from homocysteine (folate and B12 are cofactors )
- homocysteine to cysteine
(requires two vitamin B6-dependent enzymes - overall homocysteine in the blood is regulated by folate, B12, and B6
How is folate absorbed?
PCFT (proton-coupled folate transporter) is the mechanism by which folates are absorbed across the apical brush-border membrane of the small intestine.
Folate is absorbed in the jejunum (SI)
Conjugase converts polyglutatamate (form consumed in dietary folate) and is deconjugated to monoglutamate.
Monoglutamate goes into the blood in the form of methyltetrahydrofolate (MTHF)
How is folic acid absorbed?
Folic acid is significantly more bioavailable than naturally occurring dietary folates due to it being fully oxidized (natural folates are reduced molecules).
Folic acid (oxidized) is reduced in the intestine to THF in the intestine
Step 1: folic acid
Step 2: DHF (dihydrofolate)
Step 3: THF (tetrahydrofolate)
How and where does folic acid enter the folate cycle?
Dietary folic acid enters the folate cycle via the tetrahydrofolate (THF) in the intestine
5’methyl-THF
It enters there because this is the form that is in your blood
Food folate is reduced (oxidized)
What is Rs1801133? Why is it important to know?
Rs1801133 = C677T Rs1801133 = SNP (single nucleotide polymorphism) that encodes a variant in the MTHFR gene, which encodes an enzyme involved in folate metabolism.
The MTHFR gene provides instructions to make an enzyme called MTHFR (methylenetetrahydrofolate reductase)
What is the RDA for folic acid?
400 ug/day
anything greater than 200 ug will have folic acid in the blood
How does a B12 deficiency create a secondary folate deficiency?
Folate enters the folate cycle as 5-methyl THF and requires B12 to convert to THF
If B12 is deficient then this conversion is not able to occur and will result in subsequent folate deficiency.
Folic acid enters the folate cycle at THF which bypasses the need for B12 to convert 5-methyl-THF
Folate is the cause of megaloblastic anemia. If folate deficiency is replenished via folic acid, there will no longer be signs of megaloblastic anemia which can therefore mask a B12 vitamin deficiency which may still be present. (deficiency that is no longer presenting symptoms - could cause neurological issues)
