Folic Acid Biotechnological Production and Applications



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Folic acid (synthetic form) which also known as folate (naturally occurring form) is a member of the water soluble B complex vitamin. Folic acid is man-made. It can be found in many beans, grains, fortified breakfast cereals, pasta, and green vegetables. Folic acid plays big part in building DNA and aids the body to make new new cells, especially red blood cells. Folic acid hold general properties of water-soluble vitamin which are enter the bloodstream properties immediately after being consumed through excretion in urine. Other than that, unlike fat-soluble vitamin, they are easily destroyed in heat or by air pressure. These folic acid are absorbed into blood via portal vein to the liver.

Vitamin B9 including folic acid and folate is important for several bodily functions which are used for synthesizing and repairing DNA, RNA and , assisting rapid cell division and growth to produce healthy red blood cells. It is important for pregnant women to have enough folic acid to prevent major birth defects of her baby’s brain or spine and enhances brain health. The memory is said to be improved through folic acid consumption. The human body does not synthesize folic acid, therefore to make sure we have adequate amounts ,we should take it everyday. To reduce the number of neural tube defects there are many countries are adopted the policy of fortification of folic acid. When fortification is introduced , many people are exposed to an increased intake of folic acid .With this, neural tube defects can be prevented. For animals, diet that consists can influence DNA and histone. This leads to phenotypic changes in next generation. While for humans, the increased intake leads to elevated blood concentrations and of unmetabolized folic acid. This related to decreased natural killer cell cytotoxicity, and reduce the response to antifolate drugs used against cancer, malaria, and cancer.

Keywords : Folic acid, water-soluble vitamin,fat-soluble vitamin, methylation,antifolate


History of Folic acid

Through a research made by Indian scientist, there is connection between the macrocytic anaemia and deficiency in the diet. However, what kind of deficiency was not determined.

The name of “folic acid was suggested which coming from the Latin word for the leaf “foium”,due to a factor suspected of having vitamin-like properties in animals that was isolated from spinach.

In 1945, the importance of folic acid to treat a type of amenia during pregnancy can be seen through a demonstration. In 1962 , Dr. Victor Herbert conducted experiment on himself in order to show a shortage of folic acid caused a type of anemia.The experiment is successful. It was Dr. Herbert’s findings that set the criteria for the diagnosis of folate deficiency and the folic acid adult requirement.

Figure 1.1 Chemical Structure of Folic Acid


2.1 DNA and Cell Division

For the production DNA and RNA synthesis and maintaining new cells, folate is required. And it is also required in preventing changes to DNA, and, thus, for preventing cancer. More specifically it helps in the manufacture of nucleic acids like Thymine. A folate coenzyme is required for the synthesis of methionine, and methionine is required for the synthesis of S-adenosylmethionine (SAM). SAM is a methyl group (one-carbon unit) donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA.

2.2 Biochemistry of DNA base and amino acid production

In the form of a series of tetrahydrofolate (THF) compounds, folate derivatives are substrates in a number of single-carbon-transfer reactions, and also are involved in the synthesis of dTMP (2?-deoxythymidine-5?-phosphate) from dUMP (2?-deoxyuridine-5?-phosphate). It is a substrate for an important reaction that involves vitamin B12 and it is necessary for the synthesis of DNA and required for all dividing cells.

2.3 Conversion to biologically active derivatives

All the biological functions of folic acid are performed by tetrahydrofolate and other derivatives. Their biological availability to the body depends upon dihydrofolate reductase action in the liver. This action is unusually slow in humans. Due to this low activity, it has been suggested this limits the conversion of folic acid into its biologically active forms “when folic acid is consumed at levels higher than the Tolerable Upper Intake Level (1 mg/d for adults)


Kidney disease

About 90% of people with serious kidney disease have high levels of homocysteine. High levels of homocysteine have been linked to heart disease and stroke.By taking folic acid,it may lower homocysteine levels in people with serious kidney disease. However,through a research, folic acid supplementation are found fail to reduce the risk of heart disease-related events.

Colon Cancer

Folic acid play big role of protection for patients with the inflammatory bowel condition ulcerative colitis are particularly at risk for colon cancer. In a subsequent study, researchers examined the effects of folate on a laboratory model of colorectal cancer development in mice. They discovered that animals consuming a folate-deficient diet developed intestinal masses, while those mice on a control diet consuming adequate amounts of folate remained free of tumors. The conclusion is that folate deficiency increased DNA damage by decreasing the expression of two genes involved in DNA repair. This study is consistent with the majority of epidemiological studies in humans, which demonstrate a clear link between colorectal cancer development and inadequate folate consumption.

4 Folic Acid : The most essential nutrient for Pregnancy

Folic acid is well-known as the most essential nutrient for pregnancy. There are many studies have shown that women can reduce the risk that their baby will be born with a serious neural tube defect ( incomplete development of the brain and spinal cord) up to 70% for women who get 400 micrograms (0.4 milligrams) daily prior to conception and during early pregnancy.

The most common neural tube defects are spina bifida, an incomplete closure of the spinal cord and spinal column anencephaly, severe underdevelopment of the brain encephalocele, when brain tissue protrudes out to the skin from an abnormal opening in the skull.

It’s so important for all women of childbearing age to get enough folic acid , not just those who are planning to become pregnant, because all of these defects occur during the first 28 days of pregnancy usually before a woman even knows she’s pregnant. Through a survey, only 50% of pregnancies are planned, so any woman who could become pregnant should make sure she’s getting enough folic acid.

Folic acid has no use biochemically in the body until it is converted into these other forms of folate such as:

Tetrahydrofolate (THF)

5-formyltetrahydrofolate (Folinic acid)


5-methyltetrahydrofolate (Methylfolate


Folic acid is a form of folate. Since folate is water-soluble B vitamin, it is found naturally in foods. This vitamin cannot be synthesized in our body. Folate is important for everyone especially it helps make red blood cells. If you do not have enough folate, you can get a type of anaemia. If you have anaemia you may feel tired, weak and unable to concentrate. Folate also very important for infants, children and women who are pregnant. It helps to prevent some birth defects. Women who could become pregnant, are pregnant or breastfeeding need more folate. They should take a daily folic acid supplement of 400 mcg (0.4 mg).In addition to poor dietary intake of deficient intake of other B vitamins can contribute to folate deficiency. These vitamins include B1, B2, and B3 which are all involved in folate recycling. Poor protein intake can cause deficiency of folate binding protein which is needed for optimal absorption of folate from the intestine, and can also be related to an insufficient supply of glycine and serine, the amino acids that directly participate in metabolic recycling of folate. Excessive intake of alcohol, smoking, and heavy coffee drinking can also contribute to folate deficiency.

How much folate should everyone aim?


Aim for an intake of* (mcg/day)

Stay Below* (mcg/day)

Men and Women 19 years and older



Pregnant Women 19 years and older



Breastfeeding Women 19 years and older



Nutrient Interactions

How do other nutrients interact with folate ?

Vitamins B1, B2, and B3 must be present in adequate amounts to enable folic acid to can hide a vitamin B12 deficiency, by masking blood-related symptoms.

A Food Rating System is created in order to better help to identify foods that feature a high concentration of nutrients for the calories they contain, we created This system allows us to highlight the foods that are especially rich in particular nutrients. The following chart shows the World’s Healthiest Foods that are either an excellent, very good, or good source of folate. Next to each food name, we may find the serving size we used to calculate the food’s nutrient composition

World’s Healthiest Foods ranked as quality sources of folate


Serving Size


Amount (mcg)

DRI/DV (%)

Nutrient Density

World’s Healthiest Foods Rating


1 cup







1 cup







1 cup






Turnip Greens

1 cup







1 cup







1 cup






Table 1.2 Use the following to determine the intake of folate


Shortage of folic acid can cause severe health problems in offspring, including anaemia, cardiovascular and liver diseases. A study out today revealed that the metabolism of folic acid not only impacts the immediate offspring but can also have detrimental health effects on the next several generations due to a mutation in a gene necessary. The new research, which also focus on the molecular mechanism of folic acid.

The damaging effects of folic acid deficiency on development are quite renowned. This is demonstrated t by the researchers, from the Universities of Cambridge and Calgary. They used mice in this experiment as they metabolize folic acid very similarly to humans, because folic acid deficiency or mutations in the same genes required to break down folic acid in humans result in similar developmental abnormalities and diseases in mice. This enables the researchers to analyze the effects of how the molecular mechanism of folic acid deficiency impacted development that causing health problems.

Other than that, inadequate in either B12 or folate can lead to macrocytic anaemia, a disease which red blood cell are larger than normal. It characterized by the production of fewer but larger red blood cells, thus a reduce ability to carry oxygen. Those affected may be weak, light-headed, and short of breath due to anemia. A deficiency in B12 can also result in varying degrees of neuropathy or nerve damage .The symptoms of lack of B12 can cause itchy and numbness in the person’s hands and feet. In severe cases, mental changes that range from confusion and irritability to dementia may appear.

For proper foetal development, pregnant women need sufficient amounts of folate.Increased amounts of folate required because of the added stress of rapidly growing cells (the foetus), If a woman has a folate deficiency during pregnancy, it will be quicken during gestation and may lead to premature birth and neural tube birth defects, such as spina bifida, in the child. The number of neural tube defect cases decreased by 36% in the U.S. since focusing on folate supplements during pregnancy. Restless leg syndrome during pregnancy is another neurologic symptom associated with decreased folate.

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