These are the pteridine ring, para-amino benzoic acid, and glutamic acid. CopyCopied, CSID:5815, http://www.chemspider.com/Chemical-Structure.5815.html (accessed 13:07, Jan 25, 2021) [11], In 1996, the United States Food and Drug Administration (FDA) published regulations requiring the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products. Folic acid is synthesized by bacteria from the substrate, para-amino-benzoic acid (PABA), and all cells require folic acid for growth. [72] Research found a link between depression and low levels of folate. Folate, also known as vitamin B9 and folacin,[6] is one of the B vitamins. [9] It occurs naturally in many foods. Last updated on Sep 3, 2020. The antifolate drug methotrexate is often used to treat cancer because it inhibits the production of the active tetrahydrofolate (THF) from the inactive dihydrofolate (DHF). [129] This could be from the fact that many foods are fortified by 160–175% over the required amount. [3] Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby. Its chemical structure contains three distinct parts, consisting of glutamic acid, a para-aminobenzoic acid (PABA) residue and a pteridine nucleus (Illus. Folic acid is also used for other conditions commonly associated with folate deficiency, including ulcerative colitis, liver disease, alcoholism, and kidney dialysis. Cats with exocrine pancreatic insufficiency, moreso than dogs, may have low serum folate. One-carbon units in a variety of oxidation states may be attached to the N5 nitrogen atom of the pteridine ring and/or the N10 nitrogen atom of the p-aminobenzoyl group.[25]. [114] New Zealand was also planning to fortify bread (excluding organic and unleavened varieties) starting in 2009, but then opted to wait until more research was done. März 2007: Quelle: Self-made in BKChem + perl + vim. [73][74] The exact mechanisms involved in the development of schizophrenia and depression are not entirely clear, but the bioactive folate, methyltetrahydrofolate (5-MTHF), a direct target of methyl donors such as S-adenosyl methionine (SAMe), recycles the inactive dihydrobiopterin (BH2) into tetrahydrobiopterin (BH4), the necessary cofactor in various steps of monoamine synthesis, including that of dopamine. Stay tuned with BYJU’S for more scientific information about chemical components!! Datum: 10. [2], Bob Stokstad isolated the pure crystalline form in 1943, and was able to determine its chemical structure while working at the Lederle Laboratories of the American Cyanamid Company. [82] This series of reactions using the β-carbon atom of serine as the carbon source provide the largest part of the one-carbon units available to the cell. View information & documentation regarding Folic acid, including CAS, MSDS & more. [8][83] Mechanistically, hydride is transferred from NADPH to the C6 position of the pteridine ring. Generic Name: Folic Acid, Vitamin B6, Vitamin B12, Omega-3 Acids, and Phytosterols (FOE lik AS id/VYE ta min/oh MAY ga 3 AS ids/fi to STER ols) Brand Name: BP Vit 3, Taliva, Vitamez Medically reviewed by Drugs.com. People with megaloblastic anemia need to be tested for vitamin B12 deficiency before treatment with folic acid, because if the person has vitamin B12 deficiency, folic acid supplementation can remove the anemia, but can also worsen neurologic problems. There is evidence that folate consumption is protective. "folates") are acceptors and donors of one-carbon units for all oxidation levels of carbon (except for the most oxidized form - CO2. A serum folate of 3 μg/L or lower indicates deficiency. [26] Folate deficiency is diagnosed by analyzing a complete blood count (CBC) and plasma vitamin B12 and folate levels. The reason for the difference is that when folic acid is added to food or taken as a dietary supplement with food it is at least 85% absorbed, whereas only about 50% of folate naturally present in food is absorbed. CLINICAL PHARMACOLOGY . [47][48] The beneficial effect was larger in the subset of trials that used a lower folic acid supplement compared to higher. [38], Folic acid is added to grain products in more than 80 countries, either as required or voluntary fortification,[11][36] and these fortified products make up a significant source of the population's folate intake. 6 and folic acid was obtained by diluting 0.4 ml of standard stock solution of B 1, 0.8 ml of standards stock solution of B 3, 0.2 ml of standard stock solution of B 6 and 0.8 ml of standard stock solution of folic acid to 10 ml with 15 % methanol solution. [135] In 1931, researcher Lucy Wills made a key observation that led to the identification of folate as the nutrient required to prevent anemia during pregnancy. [53] For prostate cancer risk, comparing low to high dietary folate showed no effect,[54][55] but the same two studies reported a significant increased risk for prostate cancer correlating to elevated serum folate. [100] The Japan National Institute of Health and Nutrition set the adult UL at 1,300 or 1,400 μg depending on age. [87], A number of drugs interfere with the biosynthesis of THF from folic acid. Folic Acid Tablets, USP 1 mg contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate and stearic acid. Leafy vegetables such as spinach, turnip greens, lettuces, dried beans and peas, fortified cereal products, sunflower seeds and certain other fruits and vegetables are rich sources of folate. Because the neural tube closes in the first four weeks of gestation, often before many women even know they are pregnant, many countries in time decided to implement mandatory food fortification programs. Folinic acid is an adjuvant used in cancer chemotherapy involving the drug methotrexate. a methyl group, methylene group, or formyl group). Serum folate reacts more rapidly to folate intake than erythrocyte folate. Some of these large cells, although immature (reticulocytes), are released early from the marrow in an attempt to compensate for the anemia. A table of selected food sources of folate and folic acid can be found at the USDA National Nutrient Datab… [102] One theory is that consumption of large amounts of folic acid leads to detectable amounts of unmetabolized folic acid circulating in blood because the enzyme dihydrofolate reductase that converts folic acid to the biologically active forms is rate limiting. [33], Deficiency of folate in pregnant women has been implicated in neural tube defects (NTDs), with an estimate of 300,000 cases worldwide prior to the implementation in many countries of mandatory food fortification. [45][46], The absolute risk of stroke with supplementation decreases from 4.4% to 3.8% (a 10% decrease in relative risk). [28] Cobalamin (vitamin B12) deficiency may lead to folate deficiency, which, in turn, increases homocysteine levels and may result in the development of cardiovascular disease or birth defects. A meta-analysis of global birth prevalence of spina bifida showed that when mandatory fortification was compared to countries with voluntary fortification or no fortification program, there was a 30% reduction in live births with spina bifida. This translates to an annual saving in total direct costs of approximately $508 million for the NTD-affected births that were prevented. Liver and liver products also contain high amounts of folate, as does baker's yeast. The molecular structure is based on structures generated from information available in ECHA’s databases. [16] The term "folic" is from the Latin word folium (which means leaf) because it was found in dark-green leafy vegetables. ;Target: AntifolateFolinic acid is a 5-formyl derivative of tetrahydrofolic acid. The biologically active form is reduced tetrahydrofolates, serving as an essential cofactor in methylation reactions, including the vitamin B12-dependent formation of methionine from homocysteine, and as a carrier of one-carbon units involved in the synthesis of purines and pyrimidines. Some cereals contain 100% of the daily value of folic acid a woman should take per day. Folic acid has a molecular structure that is nearly identical to folate. One potential issue associated with high doses of folic acid is that it has a masking effect on the diagnosis of pernicious anaemia due to vitamin B12 deficiency, and may even precipitate or exacerbate neuropathy in vitamin B12-deficient individuals. [12][47] The effect was also larger for the studies that were conducted in countries that did not have mandatory grain folic acid fortification. [59] However, methotrexate can be toxic,[60][61][62] producing side effects such as inflammation in the digestive tract that make eating normally more difficult. Formyl folate is required for two of the steps in the biosynthesis of inosine monophosphate, the precursor to GMP and AMP. [1][28] The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. The second study reported no significant increase or decrease in total cancer incidence, colorectal cancer, other gastrointestinal cancer, genitourinary cancer, lung cancer or hematological malignancies in people who were consuming folic acid supplements. [6][18][19][20] Historic names included L. ⁠casei, factor vitamin Bc and vitamin M.[2], The terms "folate" and "folic acid" have somewhat different meanings in different contexts, although sometimes used interchangeably. [1] More than 80 countries use either mandatory or voluntary fortification of certain foods with folic acid as a measure to decrease the rate of NTDs. [34] NTDs occur early in pregnancy (first month), therefore women must have abundant folate upon conception and for this reason there is a recommendation that any woman planning to become pregnant consume a folate-containing dietary supplement before and during pregnancy. [36] The most commonly fortified vitamin – as used in 62 countries – is folate; the most commonly fortified food is wheat flour, followed by maize flour and rice. [27], Folate deficiency may lead to glossitis, diarrhea, depression, confusion, anemia, and fetal neural tube and brain defects. Dies gilt weltweit. In dog breeds at risk for cleft lip and cleft palate dietary folic acid supplementation significantly decreased incidence. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), and, thus, has vitamin activity that is equivalent to that of folic acid. 12-1). It was first isolated via extraction from spinach leaves by Herschel K. Mitchell, Esmond E. Snell, and Roger J… [51] However, at blood concentrations achieved via food fortification, folic acid has no known cofactor function that would increase the likelihood of a causal role for free FA in disease development. For folate, 100% RI was set at 200 μg in 2011.[109]. [28] Serum folate level reflects folate status, but erythrocyte folate level better reflects tissue stores after intake. [1], Not consuming enough folate can lead to folate deficiency. RNA transcription and subsequent protein synthesis are less affected by folate deficiency, as the mRNA can be recycled and used again (as opposed to DNA synthesis, where a new genomic copy must be created). Folic acid is a type of B vitamin that is normally found in foods such as dried beans, peas, lentils, oranges, whole-wheat products, liver, asparagus, beets, broccoli, brussels sprouts, and spinach. CopyCopied, OVBPIULPVIDEAO-LBPRGKRZSA-N [68][67][69], A 2017 meta-analysis found that the relative risk of autism spectrum disorders was reduced by 23% when the maternal diet was supplemented with folic acid during pregnancy. [3] Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. folic acid. In case of you suffer from folic acid deficiency, the form of DNA will become abnormal and this will lead to cervical dyslapsia. The requirement was set at 135 µg of folate per 100 g of bread. Folate is especially important during periods of frequent cell division and growth, such as infancy and pregnancy. Due to their close resemblance, folic acid and folate are widely considered to b… Among them are the antifolate dihydrofolate reductase inhibitors such as the antimicrobial, trimethoprim, the antiprotozoal, pyrimethamine and the chemotherapy drug methotrexate,[88][89] and the sulfonamides (competitive inhibitors of 4-aminobenzoic acid in the reactions of dihydropteroate synthetase). [104] Long-term use of folic acid dietary supplements in excess of 1,000 μg/day has been linked to an increase in prostate cancer risk.[13]. [28] Other symptoms include fatigue, gray hair, mouth sores, poor growth, and swollen tongue. [12][47] The beneficial result may be associated with lowering circulating homocysteine concentration, as stratified analysis showed that risk was reduced more when there was a larger decrease in homocysteine. For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). Some breakfast cereals (ready-to-eat and others) are fortified with 25% to 100% of the recommended dietary allowance (RDA) for folic acid. [47][48] Two of these three were limited to people with pre-existing cardiovascular disease or coronary heart disease. [12] Two older meta-analyses, which would not have incorporated results from newer clinical trials, reported no changes to the risk of cardiovascular disease. Subset analysis confirmed this among Asian, European and American populations. [36], Australia and New Zealand jointly agreed to wheat flour fortification through the Food Standards Australia New Zealand in 2007. [56] Supplementation with folic acid at 1,000 to 2,500 μg/day – the amounts used in many of the supplement trials[13][56] – would result in higher concentrations of serum folate than what is achieved from diets high in food-derived folate. … The crystal and molecular structure of folic acid dihydrate has been determined by x-ray diffraction. The most commonly mandatory fortified vitamin – in 62 countries – is folate; the most commonly fortified food is wheat flour. Folic acid derivatives (i.e. A 2018 review by authors based in the United Kingdom strongly recommended that mandatory fortification be reconsidered as a means of reducing the risk of neural tube defects. [56] A third supplementation meta-analysis limited to reporting only on colorectal cancer incidence showed that folic acid treatment was not associated with colorectal cancer risk.[57]. However, folic acid cannot cross bacterial cell walls by diffusion or active transport. [31][32], Increased homocysteine levels suggest tissue folate deficiency, but homocysteine is also affected by vitamin B12 and vitamin B6, renal function, and genetics. Folate is the common form of vitamin B9 present in many whole foods, including leafy greens, beans, eggs, citrus fruit, avocados, and beef liver. [52] The results of folic acid fortification on the rate of neural tube defects in Canada have been positive, showing a 46% reduction in prevalence of NTDs; the magnitude of reduction was proportional to the prefortification rate of NTDs, essentially removing geographical variations in rates of NTDs seen in Canada before fortification. [119] Folic acid food fortification became mandatory in 1998, with the fortification of 150 µg of folic acid per 100 grams of enriched flour and uncooked cereal grains. [47][48], Chronically insufficient intake of folate may increase the risk of colorectal, breast, ovarian, pancreas, brain, lung, cervical, and prostate cancers. Countries have implemented either mandatory or voluntary food fortification of wheat flour and other grains,[36] or else have no such program and depend on public health and healthcare practitioner advice to women of childbearing age. Lizenz . [98] The United Kingdom's Dietary Reference Value for folate, set by the Committee on Medical Aspects of Food and Nutrition Policy in 1991, is 200 μg/day for adults. [30] Both adults and children need folate to make normal red and white blood cells and prevent anemia, which causes fatigue, weakness, and inability to concentrate. BH4 serves a regulatory role in monoamine neurotransmission and is required to mediate the actions of most antidepressants. Excessive amounts derived from supplements are more of a concern than that derived from natural food sources and the relative proportion to vitamin B12 may be a significant factor in adverse effects. In the US, mandatory fortification of enriched breads, cereals, flours, corn meal, pastas, rice, and other grain products began in January 1998. Folacin is the generic descriptor not only for the original vitamin, folic acid, but also for related compounds that qualitatively show folic acid activity; the pure substance being designated pterylomonoglutamic acid. [44], One meta-analysis reported that multi-year folic acid supplementation, in amounts in most of the included clinical trials at higher than the UL of 1,000 μg/day, reduced the relative risk of cardiovascular disease by a modest 4%. 1D NMR Spectrum 1092 - Folic acid (HMDB0000121) 1D NMR Spectrum 2513 - Folic acid (HMDB0000121) 1D NMR Spectrum 3211 - Folic acid (HMDB0000121) 1D NMR Spectrum 5134 - Folic acid (HMDB0000121) 1D NMR Spectrum 5135 - Folic acid (HMDB0000121) [19], A meta-analysis of folate supplementation during pregnancy reported a 28% lower relative risk of newborn congenital heart defects. N N N NH2 N OH CH2 NH C NH CH O CO2H CH2 CH2 COOH N N H N N H OH NH2 NADPH DHFA reductase = H H CH2 H NH R THFA • Other "conjugates" of DHFA and THFA that have more than [24], Chemically, folates consist of three distinct chemical moieties linked together. [90], Valproic acid, one of the most commonly prescribed epilepsy treatment drugs, also used to treat certain psychological conditions such as bipolar disorder, is a known inhibitor of folic acid, and as such, has been shown to cause birth defects, including neural tube defects, plus increased risk for children having cognitive impairment and autism. [135] In 1960, researchers linked folate deficiency to risk of neural tube defects. Hence folic acid must first be reduced to THF. RDAs. [141], Vitamin B9; nutrient essential for DNA synthesis, n1c2C(=O)NC(N)=Nc2ncc1CNc3ccc(cc3)C(=O)N[C@H](C(O)=O)CCC(O)=O, InChI=1S/C19H19N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1, World Health Organization's List of Essential Medicines, United States Preventive Services Task Force, Centers for Disease Control and Prevention, "Fact Sheet for Health Professionals – Folate", "Contemporary issues surrounding folic Acid fortification initiatives", "Public health failure in the prevention of neural tube defects: time to abandon the tolerable upper intake level of folate", "Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials", "Cancer risk with folic acid supplements: a systematic review and meta-analysis", "Nomenclature and symbols for folic acid and related compounds", "Toward a better understanding of folate metabolism in health and disease", "Folate deficiency: MedlinePlus Medical Encyclopedia", "Folate and Your Health – HealthLinkBC File #68g", "Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies", "Map: Count of Nutrients In Fortification Standards", "Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis", "Impact of folic acid fortification of flour on neural tube defects: a systematic review", "Maternal folic acid supplementation and the risk of congenital heart defects in offspring: a meta-analysis of epidemiological observational studies", "Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation", "Maternal antenatal multiple micronutrient supplementation for long-term health benefits in children: a systematic review and meta-analysis", "Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis", "The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility", "Null association between prostate cancer and serum folate, vitamin B(6), vitamin B(12), and homocysteine", "Folic-acid fortification of flour and increased rates of colon cancer", "A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis", "Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer", "Folate intake, serum folate levels, and prostate cancer risk: a meta-analysis of prospective studies", "Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials", "Effect of glutamine on methotrexate efficacy and toxicity", "Nutritional folate status influences the efficacy and toxicity of chemotherapy in rats", "The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis", "Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review", "Is low folate a risk factor for depression? [79], The biological activity of folate in the body depends upon dihydrofolate reductase action in the liver which converts folate into tetrahydrofolate (THF). This four electron reduction proceeds in two chemical steps both catalyzed by the same enzyme, dihydrofolate reductase. The structure of folic acid is shown in Figure 7. [97] This historical research project, of obtaining folic acid in a pure crystalline form in 1945, was done by the team called the "folic acid boys," under the supervision and guidance of Director of Research Dr. Yellapragada Subbarow, at the Lederle Lab, Pearl River, NY. [82] Folic acid is first reduced to dihydrofolate and then to tetrahydrofolate. [38] The United States Preventive Services Task Force recommends folic acid as the supplement or fortification ingredient, as forms of folate other than folic acid have not been studied. ChEBI Name folic acid: ChEBI ID CHEBI:27470: Definition An N-acyl-amino acid that is a form of the water-soluble vitamin B 9.Its biologically active forms (tetrahydrofolate and others) are essential for nucleotide biosynthesis and homocysteine remethylation. [81], All of the biological functions of folic acid are performed by THF and its methylated derivatives. [127], The fortification program was expected to raise a person's folic acid intake level by 70–130 µg/day;[128] however, an increase of almost double that amount was actually observed. FR page 33982", "Daily Value Reference of the Dietary Supplement Label Database (DSLD)", "Industry Resources on the Changes to the Nutrition Facts Label", "Regulation (EU) No 1169/2011 of the European Parliament and of the Council", "Folate content in micrograms per 100 g, All Foods; USDA Food Composition Databases", "Work Starts on Wilkinson's Mass Medication Plan", "NZ should push pause on folic fortification", "Board recommends mandatory fortification", "Food and Drug Administration. Folic Acid Structural Formula. [125] This ruling took effect on 1 January 1998, and was specifically targeted to reduce the risk of neural tube birth defects in newborns. As of the 27 May 2016 update, it was kept unchanged at 400 μg. [110] The Food Fortification Initiative lists all countries in the world that conduct fortification programs,[111] and within each country, what nutrients are added to which foods, and whether those programs are voluntary or mandatory. [22][20] Within the field of biochemistry, folates refer to a class of biologically active compounds related to and including folic acid. [103], The U.S. National Center for Health Statistics conducts the biannual National Health and Nutrition Examination Survey (NHANES) to assess the health and nutritional status of adults and children in the United States. [70], Some evidence links a shortage of folate with clinical depression. One DFE is defined as 1 μg of dietary folate. IPR-MUS LD50 85 mg kg-1, IVN-GPG LD50 120 mg kg-1, IVN-MUS LD50 239 mg kg-1, IVN-RAT LD50 500 mg kg-1, IVN-RBT LD50 410 mg kg-1, Organic Compound; Amine; Amide; Ester; Drug; Hematinic; Vitamin B Complex; Food Toxin; Dietary Supplement; Micronutrient; Metabolite; Nutraceutical; Household Toxin; Fungal Toxin; Natural Compound; Supplement, CAUTION: May irritate eyes, skin, and respiratory tract. [1] This may result in a type of anemia in which red blood cells become abnormally large. Methylenetetrahydrofolate donates the C1 center required for the biosynthesis of dTMP (2′-deoxythymidine-5′-phosphate) from dUMP (2′-deoxyuridine-5′-phosphate). Folic acid(Vitamin M; Vitamin B9) is a B vitamin; is necessary for the production and maintenance of new cells, for DNA synthesis and RNA synthesis. The chemistry symbols of this structural formula are drawn using the path text method. This is a concern because 70–80% of the population have detectable levels of unmetabolized folic acid in their blood, a consequence of folic acid supplementation and fortification.

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