SDSU Biology Discussion

Reply 1:
From this discussion prompt, I can use major points with thoughtful analysis to
support my response. To describe the metabolism of folate, humans do not specifically
synthesize folate and must obtain folate from their diet. In more details, the folate
molecule is synthesized from para-aminobenzoic acid and pterin pyrophosphate
through the action of dihydrofolate synthase. Derived in a series of enzymatically
catalyzed steps from guanosine triphosphate (GTP), pterin occurs and the paraaminobenzoic acid is the product of shikimate pathway. To enumerate the metabolism
of folate, dihydrofolate reductase is located in the liver which converts folate into
tetrahydrofolate (THF). As the rate-limiting reaction in humans, this leads to elevated
blood concentrations of unmetabolized folic acid when consumed in fortified foods near
the U.S. Tolerable Upper Intake Level of 1,000 μg per day. 2 Specifically, tetrahydro folic
acid is the active form of folate that serves to respond to one carbon reduction reaction.
With this said, these reactions are correlated to the synthesis of nucleotides and amino
acids. In fact, tetrahydro folic acid is the active form of folate and serves to respond to
one carbon reduction reaction. From above, it is important to know that the enzyme
responsible for conversion is dependent on riboflavin (B3) and particular level
interactions are involved. Several level interactions between B vitamins are required for
DNA synthesis. With this said, folic acid is required for erythropoiesis and therefore folic
acid deficiency will lead to megaloblastic anemia.
In addition to the metabolism of folate, the biochemical uses in humans involve the
function of folate acting as vitamin B9 and naturally occurring in foods. These foods
involve vegetables, beans, fruit, green leafy, and citrus. Folate has the function of
helping tissues grow and cells work. In particular, it works with vitamin B12 and vitamin
C to help the body break down, use, and create new proteins. Also, it helps in the
synthesis of DNA precursors, purines, and pyrimidines and in the formation of red blood
cells. From above, we know that THF is the coenzyme of folic acid and is involved in the
one-carbon metabolism. Serving as an acceptor or donor of one-carbon units, THF
helps in reactions involving amino acid and nucleotide metabolism.
Next, I will highlight the causes and consequences of its deficiency. In more details,
folic acid deficiency results in decreased production of purines and dTMP which impairs
DNA synthesis. From a block in DNA synthesis, erythrocyte maturation is slowed down
which results in macrocytic RBC. With the abnormally large RBC, the macrocytic
anemia is associated with megaloblastic bone marrow that changes a characteristic
feature of folate deficiency. In particular, in pregnant women the folic acid deficiency
may lead to neural defects in the fetus with high doses of folic acid. 1 To elaborate on
folic acid, it is associated with the metabolism of histidine that forms
formiminoglutamate. In this case of folic acid deficiency, FIGLU accumulates and is
excreted in the urine that may cause diarrhea, mouth ulcers, peptic ulcer, poor growth,
and certain types of anemias.
Lastly, I will cover the causes of folate deficiency. With the knowledge of folate being
a water-soluble, this is a specific vitamin that isn’t stored in fat cells. Excess amounts of
water-soluble vitamins are released in the urine and the causes of folate deficiency
include a few key components. These involve fortified cereals, vegetables, and a diet
low in fresh fruits. 1 As a result, diseases that affect absorption in the gastrointestinal
tract include Crohn’s disease, severe kidney problems, celiac disease, and particular
types of cancers. In more detail, genetic mutations may hinder the body from properly
converting dietary folate to its usable form, methyl folate. There are specific medications
like phenytoin, methotrexate, sulfasalazine, and trimethoprim-sulfamethoxazole that can
cause folate deficiency. In addition, excessive alcohol intake can affect the folate
absorption and increase folate exception through the urine.
References
1.Hamid A, Wani NA, Kaur J (April 2009). “New viewpoints on folate transport according
to liquor addiction actuated folate malabsorption-relationship with epigenome
dependability and disease improvement”. The FEBS Diary. 276 (8): 2175-91.
2.Lohner S, Fekete K, Berti C, Hermoso M, Cetin I, Koletzko B, Decsi T (December
2012). “Impact of folate supplementation on folate status and wellbeing results in
babies, youngsters and youths: an orderly survey”. Global Diary of Food Sciences and
Nourishment. 63 (8)
Reply 2 :
Folate metabolism is critical to help our bodies carry out normal processes. Folate is the
naturally occurring form of vitamin B9. It is water-soluble, and it is found in many foods
naturally. It is also added to foods in its synthetic form, folic acid. Folate plays a role in
helping red blood cells divide and proliferate, preventing congenital disabilities, reducing
the risk of cancer and heart disease, and helping the body utilize amino acids. Green
leafy vegetables such as broccoli, spinach, and asparagus are rich in folate. A folate
deficiency can lead to developmental problems, anemia, and vitamin deficiencies.
Folate metabolism is a complex process that regulates amino acid changes, DNA
methylation, and nucleotide synthesis. The molecular structure of natural folate consists
of pteridine, para-aminobenzoic acid (PABA), and multiple glutamates.1 The synthetic
form only contains one molecule of glutamate. To be absorbed, folate must be in its
monoglutamate form. Mucosal folate conjugase will hydrolyze all but one glutamate in
the small intestine.2 Before folate can be transported through the bloodstream, and it
must first be reduced to its active form, tetrahydrofolate (FH4). This reduction utilizes
two molecules of NADPH and is catalyzed by dihydrofolate reductase. Folate is
transported through the bloodstream to the liver and other cells in the form of 5methyltetrahydrofolate (5-methyl THF).1 FH4 can contribute to DNA metabolism, amino
acid synthesis, and purine synthesis because of the many oxidations states it can hold
one-carbon groups. Serine is the primary carbon source for the FH4 one-carbon
pool.3 Other carbon sources include glycine, formate, and histidine.
Many processes in the human body are possible because of folate metabolism. Folate
plays many roles in cellular development, especially in embryogenesis. FH4 serves as a
carbon source for synthesizing purines involved in DNA and RNA synthesis. 2 The
conversion of homocysteine to methionine is also dependent on folate. It also plays a
role in epigenetic modifications by promoting methylation reactions. 4
Being deficient in folate can result from a variety of mechanisms. A folate deficiency can
result from dietary insufficiencies, alcohol or drug-induced, or result from germline
mutations in DHFR or SLC46A1.4 In some cases, the methylenetetrahydrofolate
reductase (MTHFR) gene is mutated, which leads to the accumulation of homocysteine.
Folate is absorbed in the jejunum, so diseases affecting the small intestine may prevent
folate absorption. Medications such as methotrexate may lead to a folate deficiency by
preventing folate absorption or inhibiting its conversion to its active form.5 When vitamin
B12 is deficient, methionine synthase can not work correctly. This can lead to a folate
deficiency because methyltetrahydrofolate will be trapped, and excess folate will be
excreted.4
Folate deficiencies can affect a variety of normal physiology in the human body.
Hyperhomocysteinemia can result when homocysteine accumulates because of a
deficiency in folate or vitamin B12. Having hyperhomocysteinemia increases the risk of
developing cardiovascular diseases and osteoporosis. In the first few weeks of
pregnancy, folate is utilized in cell division and DNA synthesis in the forming of the brain
and spinal cord.1 Folate deficiencies of any origin can lead to neural tube defects such
as spina bifida and anencephaly. A folate deficiency affects nucleic acid synthesis,
which impairs blood cell synthesis, leading to anemia. Megaloblastic anemia is one of
the most common complications of a folate deficiency.2 Impaired DNA synthesis due to
folate deficiency can put people at a greater risk for developing cancer.
Overall, folate is an essential vitamin that plays many roles in human physiology. It
helps promote growth and development starting at conception. It may have portative
effects of preventing cancer by regulating cell division. It is essential to consume
enough folate in either its natural or synthetic form.
References
1. Blake JS, Munoz KD, Volpe S. Nutrition: From Science to You. 4th ed. NY, NY.
Pearson; 2019.
2. Rosenthal MD, Glew RH. Medical biochemistry human metabolism in health and
disease. Hoboken, N. J: Wiley; 2009.
3. Tjong E, Dimri M, Mohiuddin SS. Biochemistry, Tetrahydrofolate. In: StatPearls.
Treasure Island (FL): StatPearls Publishing; July 22, 2021.
4. Zheng Y, Cantley LC. Toward a better understanding of folate metabolism in health
and disease. J Exp Med. 2018;216(2):253266. https://doi.org/10.1084/jem.20181965.
5. Khan KM, Jialal I. Folic Acid Deficiency. In: StatPearls. Treasure Island (FL):
StatPearls Publishing; September 28, 2021.

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