folate Flashcards
What is folate also known as?
Vitamin B9
What are sources of folate? what is the RDI based off?
Plant sources: Dark green leafy vegetables (spinach, kale), legumes (lentils, beans), fruits (oranges, avocados).
Animal sources: Liver, eggs, dairy products.
Fortified foods: Cereals, grains, and synthetic folic acid supplements.
-the RDI is based off the amount of folate that can maintain folate levels in RBC
How does the bioavailability of food folate compare to synthetic folic acid?
Food folate: Less than 50% bioavailable due to polyglutamate form and losses during digestion.
Synthetic folic acid: 1.7 times more bioavailable because it is already in monoglutamate form.
How is folate stored in the body? how is it transported?
In polyglutamate form, which enhances retention within cells but must be converted to monoglutamate for absorption/transportation
What are the 3 metabolic functions of folate?
1) methylation rxns
2) Nucleic acid synthesis
3) Amino acid metabolism
what is the primary active form of folate? how is it created? what enzyme is involved?
Tetrahydrofolate (THF)
1) Conversion of Folic acid into Dihydrofolate (DHF) using dihydrofolate reductase (DHFR)
2) Conversion into tetrahydrofolate using DHFR
What is the general pathway of folate metabolism?
1) Folate is ingested as polyglutamate and converted to monoglutamate for absorption.
2) Transported in the blood as 5-methyltetrahydrofolate (5-MTHF).
3) Converted inside cells into various active folate derivatives.
4) Used in DNA synthesis, amino acid metabolism, and methylation reactions.
what is THF converted into in the folate cycle? what enzyme is involed?
converted into 5,10-methylene tetrahydrofalate
-serine hydroxymethyltransferase (SHMT) is used
why is the generation of 5-methyl tetrahydrofolate important? how is this done? what is the impact of 5-MTHF deficiency?
The creation of 5-methyltetrahydrofolate is needed because 5-MTHF is needed to remove methionine from homocysteine
-generation of methionine causes methylation rxn’s
-without 5-MTHF homocysteine accumlation would occur, increasing CVD and neurodegenerative disorder risks
Methylenetetrahydrofolate reductase (MTHFR) is used to convert 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate
what are the structural properties of folate?
Folate has a polyglutamate structure (storage form) and can also be found as a monoglutamate structure
-easier to transport monoglutamate
N-5 and N-10 positions allow for 1-C substituents to bind
What are the three major folate derivatives and their functions?
1) Tetrahydrofolate (THF) – Accepts one-carbon units for metabolism
2) 5,10-Methylene-THF – Used in DNA synthesis (thymidine formation)
3) 5-Methyl-THF (5-MTHF) – Required for homocysteine → methionine conversion
How is folate involved in histidine metabolism? what occurs with a folate deficiency?
1) Histidine is converted to formiminoglutamate (FIGLU)
2) FIGLU donates a formimino group to THF, forming 5,10-methenyl-THF
Folate deficiency leads to FIGLU accumulation, which is used as a diagnostic marker for folate status
What role does folate play in pyrimidine synthesis? what else is generated? what enzyme is involved?
N5,N10-methylene-THF donates a methyl group required to convert dUMP to dTMP, generating DHF + dTMP (pyrimidine used in DNA synthesis)
-thymidylate synthetase
How is the DHF from the generation of dTMP converted back to N5,N10-Methylene-THF?
1) conversion to THF by dihydrofolate reductase (DHFR)
2) conversion to N5,N10-Methylene-THF by serine hydroxymethyl transferase
How does methotrexate affect pyrimidine synthesis?
-Inhibits dihydrofolate reductase (DHFR), preventing the conversion of DHF → THF,
-Traps DHF in the cell
-Prevents use of N5,N10-methylene-THF from being used to methylate
-blocks DNA replication
-effective chemotherapy drug.
What is the role of folate in purine synthesis? what purines does it affect? what type of enzyme is involved?
10-formyl-THF, donates formyl groups required for the synthesis of adenine (AMP) and guanine (GMP) nucleotides using a transformylase
How does the production of methionine cause methylation reactions to occur?
Methionine is used to produce S-adenosylmethionine (SAM)/AdoMet, a primary methyl donor
what vitamin is needed for the generation of methionine?
B12
How is THF converted into 5,10-methylene-THF? what vitamin is involved? what aa are needed? how is this rxn involved in the methionine cycle?
a mehtylene group is donated from serine to generate 5,10-methylene-THF
-uses B6 as a cofactor
this reaction is needed generate 5,10-methylene-THF, which is converted to methyl-THF, which is used to donate a methyl group to homocysteine, generating methionine
what is the only way our body can yield free THF?
through methionine synthase (MS)
-deamination of methyl-THF
how is PLP involced in the folate cycle?
PLP is involved in the generation of cysteine from homocysteine
how is niacin and riboflavin involved in the folate cycle?
niacin: NADPH used in the conversion of 5,10-methylene-THF to methyl-THF
riboflavin: FAD used as a prosthetic group in the same rxn
-methyl-THF reductase is the enzyme
How does folate influence epigenetics? provide 4 examples
1) DNA methylation
2) Histone methylation
3) Sterol methylation
4) Phospholipid methylation
-regulation of gene expression and cell differentiation
Insufficient folate can lead to abnormal gene activation or suppression
What is the RDI of folate for adults? pregnant women? the UL? what is this measured in
adults: 400 µg DFE/day
Pregnant: 600 µg DFE/day
UL: 1mg/day (can mask B12 deficiency)
-dietary folate equivalents
