Post 1
Introduction
Folate is a water-soluble B vitamin that cannot be produced by the human body. Folate is
a micronutrient that is required for the synthesis of both DNA and RNA, as well as for cell
development, division, growth.1 Folate can be found in leafy green vegetables, fresh fruits,
legumes, and unrefined grains. Folic acid is a biochemically inert molecule that serves as a
precursor of methyltetrahydrofolate and tetrahydrofolic acid. Methyltetrahydrofolate,
tetrahydrofolic acid, and other congeners of folic acid play a crucial role in the preservation of
normal erythropoiesis and serve as necessary cofactors for the synthesis of thymidylate nucleic
acids purine.1 They are also essential for the enzymatic conversion of amino acids, such as the
metabolic process of transforming histidine into glutamic acid, as well as the interconversion of
glycine and serine.
Molecular Mechanism
After oral ingestion, folic acid undergoes quick absorption from the small intestine. Since
dietary folate is predominantly present in the polyglutamyl form, it is necessary for it to undergo
conversion into the monoglutamate form by intestinal conjugase enzymes before it can be
absorbed.2 The monoglutamate form undergoes reduction and methylation to form
methyltetrahydrofolate, facilitated by the enzyme dihydrofolate reductase, as it is transported
across the intestinal mucosa. Folic acid in its active forms is reabsorbed via enterohepatic
recirculation. Folic acid is primarily eliminated through renal excretion as metabolites. Folic acid
is primarily eliminated through renal excretion as metabolites. When the body’s storage capacity
reaches its limit, any surplus folic acid is eliminated through the urine.
Causes of Deficiency
There are multiple ways that a person can lack folic acid. The cooking processes can
cause natural folates in food to degrade due to the variable temperatures. An induvial who does
not consume foods that have been fortified with folic acid and those who eat limited quantities of
legumes, green leafy vegetables, citrus fruits, and/or whole grains are more likely to have lower
folate levels. Conditions like hereditary folate malabsorption, celiac disease, myelofibrosis may
also cause folate deficiency. Triamterene, trimethoprim-sulfamethoxazole, and methotrexate are
drugs that inhibits the synthesis of tetrahydrofolate by interfering with the enzyme,
dihydropteroate synthetase.
Folate Deficiency
Megaloblastic anemia is brought on by a vitamin B group deficiency of folate. Folate
serves the crucial role of supplying one-carbon groups for the processes of DNA
synthesis/methylation and the epigenetic regulation of gene expression. Methylation levels in the
genome are frequently decreased by a lack of methyl donors.3 Since S-adenosylmethionine
(SAM) is a direct methyl donor, hypomethylation of the whole genome is caused by a significant
deficiency of donor methyl groups.4 While DNA methylation is mostly catalyzed and maintained
by DNMT1 during the cell division stage, it is primarily catalyzed and maintained by DNA
methyltransferases (DNMT) 3a and 3b during the embryonic stage. Given that the liver serves as
the primary location for folate storage and is consequently vulnerable to folate deficiency, the
absence of this micronutrient may potentially contribute to the occurrence of chromosomal
breaks, aneuploidy, and unfavorable modifications in gene expression within hepatocytes.
Consequently, this sequence of events can lead to genetic instability and the development of
carcinogenic processes. A diet deficient in methyl compounds, such as folate, choline, and
methionine, leads to changes in methylation patterns within the P53 gene in hepatocytes.3 These
changes have been associated with a higher likelihood of developing hepatocarcinogenesis
and/or the advancement of liver cancer.
Post 2
Folate (Vitamin B9) a water soluble vitamin that is not biosynthesized by humans. It
must be acquired in the diet and is found naturally in many foods. Folate can be added
to many foods or sold as a “folic acid” supplement. It serves many functions including
RNA and DNA formation, development and protein metabolism.1 In this forum
the metabolism, biochemical uses and deficiencies will be explored to highlight its
importance in a healthy human body.
Folate Metabolism
Before folate can be used, it has to be reduced to tetrahydrofolate (THF) by way of the
dihydrofolate reductase enzyme.2 Folate is passed through the intestine into the liver,
where two successive reduction reactions have to occur. A NADPH cofactor is involved
to donate electrons and hydrogen.1 Before folate is fully reduced to THF, 7,8dihydrofolate (DHF) forms as an intermediate. THF is transported across cells by
receptor mediated endocytosis and ultimately helps synthesize purine, interconvert
amino acids, methylate tRNA, or generate and use a formate reducing agent.3 Once
both reduction reactions are completed, THF can go through additional pathways to act
as a coenzyme in single carbon group transfer reactions. The most common derivatives
of tetrahydrofolate are: N5-methyl-tetrahydrofolate for S-adenosylmethionine synthesis (
SAM cycle), N5-N10- methylene-tetrahydrofolate for thiamine biosynthesis and N10formyl-tetrahydrofolate for purine biosynthesis. 3
Biochemical Uses
Folate is involved in crucial biochemical processes. The thymidylate (dTMP) byproduct is a metabolite required for accurate DNA genome replication.3 Biosynthesis of
purine controls cell growth, makes up essential coenzymes and donates phosphate
groups in phosphorylation reactions. Folate metabolism also allows for mitochondrial
protein translation to assist in cellular energetic balance. 2 Methionine generation is
another biochemical use as an antioxidant that detoxifies harmful substances from the
body and prevents liver damage. Folate is additionally used in making red blood cells
(RBCs). Folate is needed for the formation of heme, which is the iron containing portion
of hemoglobin in RBCs. 1
Deficiency Causes
Folate deficiency occurs with a lack of Vitamin B9 in the blood. This could be due to not
eating enough foods containing folic acid ( leafy greens, fresh fruits, whole grains),
drinking too much alcohol, pregnancy, or being on certain anti-seizure medications (
phenytoin, phenobarbital and primidone).3 A mutation of the MTHFR gene also doesn’t
allow folate to convert to THF from a hereditary standpoint. Some individuals also may
not be able to absorb folate properly due to digestive tract diseases ( celiac disease),
surgery, or some forms of cancer. 1
Deficiency Consequences
The main consequence of folate deficiency is folate deficiency anemia. As a reminder,
folate is used in the generation of RBCs. RBCs carry oxygen to all parts of the body. IN
folate deficiency anemia, the body produces abnormally large RBCs with impaired
function. 1As a result, experienced symptoms include: decreased appetite, pale skin,
diarrhea, tender tongue ,mouth ulcers, vision problems, fatigue and irritability. 2 In
pregnancy, this can lead to miscarriage or fetal deformities through a neural tube defect.
The best way to avoid these symptoms and complications are through oral
supplementation and diet. The dosage range for males and females is roughly 150 to
400 mcg daily. Pregnant female dosing can range from 400 to 800 mcg daily.3
Order an Essay Now & Get These Features For Free:
Turnitin Report
Formatting
Title Page
Citation
Outline
