Acids folic

Folic acid, or folate, is frequently mentioned as a treatment against cancer. There are many natural folate-containing foods, including leafy green vegetables and fruits such as oranges (Moss, 1992, pp. 42-44). John Heinerman also gives special mention to folic acid in his book The Treatment of Cancer with Herbs. 

In combination with vitamin B12, its more usual function is as a preventive and treatment for certain kinds of anemia, such as, pernicious anemia. More recently, it has been prominently cited for the prevention of birth defects. Its role as an enzyme inhibitor is much less publicized. 

A couple of relevant books are Folate in Health and Disease, edited by Lynn 

Bailey (1994), and Apricots and Oncogenes On Vegetables and Cancer Prevention by Eileen Jennings (1993). The latter emphasizes fohc acid and beta-carotene, and it is mentioned that fohc acid deficiency may be a major cause of colon cancer and breast cancer. It is relevant to mention here that carrots, a source of beta-carotene, are a folkloric anticancer agent, and also contain traces of bioactive alkaloids, for example, daucine, putrescine, and pyrrolidine, as well as other bioactive compounds. (Folate is commonly used as a carrier for the chanotherapy drug 5-FU, although the folate has anticancer action in itself.) 

In a study by Kearney et al. (1995) of the Department of Nutrition, Harvard School of Public Health, low folic acid levels were found to correlate with an increase in cancerous intestinal polyps, as well as with cancer in general. 

L-Fohc acid (1) contains three subunits 6-methylpterin, -aminobenzoic acid, and L-glutamic acid. The Chemicaly hstracts name is A/- [4- [ (2-amino-l,4-dihydro-4-oxo-6-pteridinyl)methyl amin o]benzoy1]-T-glutamic acid. 

Kirk-Othmer Encyclopedia of Chemical Technology (4th Edition) 

En2ymatic reduction of folic acid leads to the 7,8-dihydrofolic acid (H2 folate) (2), a key substance in biosynthesis. Further reduction, cataly2ed by the en2yme dihydrofohc acid reductase, provides (65)-5,6,7,8-tetrahydrofohc acid (H folate) (3). The folate (3) is the key biological intermediate for the formation of other folates (4—8) (Table 2). 

Fohc acid (1) is found as yellow, thin platelets which char above 250°C. The uv spectmm of L-foUc acid at pH 13 shows absorptions at A = 256 nm (e = 30, 000), 282 nm (e = 26,000), and 365 nm (e = 9800). FoHc acid has a specific rotation of [a] = +19.9 (c = 1, 0.1 NNaOH). Solutions of fohc acid are stable at room temperature and in the absence of light. It is slightly soluble in aqueous alkaU hydroxides and carbonates but is insoluble in cold water, acetone, and chloroform. Table 3 Hsts some physical properties of selected fohc acid derivatives. 

10- methylenetetiahydiofolic acid 5-formyltetiahydiofolic acid 10-formyltetiahydiofolic acid 5-fomiiminotetiahydiofolic acid 

Folic acid derivatives are usually detected using their UV absorbance at 280 nm although detection of reduced folates using amperometric detection has also been reported (Birmingham and Green, 1983). 

Folic acid functions in the transfer of one-carbon fragments in a wide variety of biosynthetic and catabolic reactions it is therefore metabolically closely related to vitamin B - Deficiency of either vitamin has similar clinical effects, and the main effects of vitamin B deficiency are exerted by effects on folate metabolism. 

Although folate is widely distributed in foods, dietary deficiency is not uncommon, and a number of commonly used drugs can cause folate depletion. More importantly. 

The extent to which the different forms of folate can be absorbed varies in order to permit calculation of folate intakes, the dietary folate equivalent has been defined as 1 Ig mixed food folates or 0.6 ig free folic acid. On this basis, total dietary folate equivalents = Ig food folate + 1.7 X synthetic (free) folic acid. 

About 80% of dietary folate is in the form of polyglutamates a variable amount may be replaced by various one-carbon fragments or be present as dihydrofolate derivatives. Folate conjugates are hydrolysed in the small intestine by conjugase (pteroyl-polyglutamate hydrolase), a zinc-dependent enzyme of the pancreatic juice, bile and mucosal brush border zinc deficiency can impair folate absorption. Free folate, released by conjugase action, is absorbed by active transport in the jejunum. 

The folate in milk is mainly bound to a specific binding protein the protein— tetrahydrofolate complex is absorbed intact, mainly in the ileum, by a mechanism that is distinct from the active transport system for the absorption of free folate. The biological availability of folate from milk, or of folate from diets to which milk has been added, is considerably greater than that of unbound folate. 

10- methylenetetiahydiofohc acid 5-formyltetiahydtofohc acid lO-formyltetrahydrofohc acid 5-fortnitninotetrahydrofohc acid 

Credit for the discovery of the nutritional significance of folic acid is often given to English medical researcher Lucy Wills (1888-1964). In the early 1920s, Wills discovered that anemia in pregnant women could be prevented if they included yeast in their diets. Anemia is a condition in which the blood contains too few red blood cells. Wills located 

Folic Acid. Red atoms are oxygen white atoms are hydrogen black atoms are carbon and blue atoms are nitrogen. Striped sticks indicate a benzene ring. 

The body produces some folic acid and obtains the remainder through food and dietary supplements. In the body, folic acid is produced by bacteria in the large intestine, absorbed in the small intestine, and stored in the liver. The 1-pteroylglutamic acid form of folic acid is also produced synthetically. 

The sole use of folic acid is as a nutrient in animal bodies. It is used in the synthesis of methionine, an amino acid used in the formation of proteins and nucleic acids. A deficiency of folic acid can produce various symptoms, including ulcers in the stomach and mouth, slowed growth, and diarrhea. It also results in a medical condition known as megaloblastic anemia, in which a person s body produces red blood cells that are larger than normal. 

Adequate amounts of folic acid are especially important in fetal development, during the first eight weeks of life following fertilization. The compound is essential to promote normal development of the fetal nervous system. Folic acid deficiencies in the mother during this period may result in neural tube defects such as spina bifida or anencephaly, a condition in which the fetus brain and skull fail to develop normally. The U.S. Centers for Disease Control and Prevention recommend that pregnant women take 600 micrograms of folic acid daily to avoid such problems. 

The 1-carbon transformations require two cofactors especially folic acid and vitamin B12. 

Several compounds that interfere with folic acid metabolism are used in clinical medicine as inhibitors of cancer cells or bacterial growth. 

Folic acid participates in the activation of single carbons and in the oxidation and reduction of single carbons. Folate-dependent single-carbon reactions are important in amino acid metabolism and in biosynthetic pathways leading to DNA, RNA, membrane lipids, and neurotransmitters. 

Therapeutic Function Treatment of B vitamin (folacin) deficiency 

Chemical Name N-[4-[ [(2-amino-1,4-dihydro-4-oxo-6-pteridinyI)methyl] amino] benzoyl] -L-glutamic acid 

Trade Name Manufacturer Country Year Introduced 

Common Name Pteroylglutamic acid Structural Formula  

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Folic acid and its derivatives (mostly the tri-and heptaglutamyl peptides) are widespread in nature. It is a specific growth ctor for certain micro-organisms, but in animals the intestinal bacteria provide the small quantities needed for growth. The coenzyme forms are actually... 

The action of the sulphonamides is antagonized by p-aminobenzoic acid and they act by inhibiting the uptake and utilization of 1-aminobenzoic acid by bacterial cells, which require this as a precursor of folic acid. 

The Schiff base obtained is converted in good yield (60 to 80%) to amines by the action of Raney Ni (209). This reductive condensation provides a good synthetic method and was used to prepare thiazole analogs (62) of folic acid (Scheme 43) (210). These Schiff bases under... 

Bacteria require p-aminobenzoic acid to biosyn thesize folic acid a growth factor Structurally sul fanilamide resembles p-aminobenzoic acid and is mistaken for it by the bacteria Folic acid biosynthesis IS inhibited and bacterial growth is slowed suffi ciently to allow the body s natural defenses to effect a cure Because animals do not biosynthesize folic acid but obtain it in their food sulfanilamide halts the growth of bacteria without harm to the host... 

At various times, antivitamin factors specific to vitamin folic acid, and choline have been reported. However, it is uncertain whether these are tme antimetaboHtes or if they may result from metaboHc interrelationships with other dietary constituents. 

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