FOLIC ACID — ptero-llmonoglutaminovy acid, biologically active compound, vitamin. Along with F. to. (see) also its derivatives, W belong to vitamins. h di - three - polyglutamates, etc., to-rye together with F. to. combine under the name «Folacinum» (ustar. synonym: B9 vitamin, vitamin of AF, vitamin M).
Main got into condition F. to. — tetrahydrofolic to - that (H4-folic to - that, tetrahydrofolate) participates as a coenzyme (see Coenzymes) in various enzymatic reactions connected with eliminating and transfer of one-carbon fragments. Thanks to it F. to. plays an important role in exchange of a number of amino acids (see) — serine, glycine, a histidine, in synthesis of methionine (see), biosynthesis of purine bases (see) and the pirimidinovy bases (see) — components of molecules of deoxyribonucleic acid (see) and RNA (see). Participation of tetrahydrofolate and other coenzymatical forms F. to. in purine exchange (see) and pirimidinovy exchange (see) defines value of this vitamin for the normal course of processes of growth, development and proliferation of fabrics, in particular for processes of a hemopoiesis and embryogenesis. In medicine F. to. and its nek-ry antimetabolites are used as pharmaceuticals. Insufficient
receipt in an organism F. to. and its derivatives leads to development patol. states. The heaviest of them are a polyneuritis (see), to a spr (see), megaloblastichesky anemia (see Anemia), etc. (see. Vitamin deficiency).
T. to. represents N-(4 [(2 amines - 4 hydroxies - 6-pteri-dpl) - methyl] - amine } - benzoyl-£ (+ ^глутаминовую to - that. Molecule F. to. consists of three parts: the replaced pterinovy cycle (2-ami-but-4-hydroxy-6-methylpterine) and the remains of paraben (see) and glutamic acid (see). T. to. contains one rest glutaminic to - you are (fig.), its conjugated forms (called sometimes «folic to - you», or «folates») as a part of the molecule contain two such rests and more (usually from 2 to 7).
Pure F. to. has an appearance of yellow fine-crystalline powder without taste p a smell with g°pl 360 °. Folic to - that is almost water-insoluble (in 100 ml of water at 0 ° 1 mg folic to - you is dissolved, at 100 ° — 50 mg), but is well dissolved in weak solutions of caustic alkalis. On light F. to. decays. A range folic to - you in 0,1 N of NaOH have three characteristic strips of absorption with maxima at 256, 283 and 365 nanometers.
T. to. the hl is quickly soaked up in proximal departments of a small bowel (especially in the presence of food masses). obr. in the form of pteroil-monoglutaminic (actually folic) to - you and in much smaller degree — a diglutamate. As folates of food are presented generally by polyglutamates with a large number of the remains glutaminic to - you, a necessary condition of their normal absorption is preliminary hydrolysis of conjugates folic to - you are a glutamate — 7'karb°ks1p1eptidaz°y (konjyu-Gaza; KF 3. 4. 12. 10), in significant amounts present at bile, juice of a pancreas, a wall of a small bowel, etc.
Transformation F. to. in its recovered coenzymatical form — tetrahydrofolate — in tissues of animals and the person occurs in two stages: on the first — F. to., attaching two hydrogen atoms, Fig. turns. A basic constitutional formula of folic acid and its conjugated forms:
I \the replaced iterp-N of an ova y a cycle (2 - amine about-4 - hydroxy - 6-metilpte-rin); II \rest of paraben; III \the rest of glutamic acid (p — number of the remains of glutamic acid in the conjugated forms of folic acid).
in a dihydrofoul the left acid, on the second — by accession
of two more hydrogen atoms H4-folic to - that is formed (tetrahydrofolate). Both reactions are catalyzed by enzyme of a digidrofolatreduktaz (KF 184.108.40.206).
The main sources of the one-carbon fragments accepted by tetrahydrofolate in reactions of a catabolism is and - carbon atom of glycine (see), ^-carbon atom of serine (see), the 2nd carbon atom them - a dicindery ring of a histidine (see), and also formed in an organism in the course of exchange reactions formic acid (see), formaldehyde (see. Ant aldehyde) and some other connections. Treat number of the one-carbon fragments transferred by tetrahydrofolate in these transformations: methyl (— CH3), methylene (— CH2 —), metinovy (— SN —-), formylation (— IT) groups and a formiminogruppa (— SN — NH). Attaching these chemical groups, tetrahydrofolate forms the following coenzymatical forms folic to - you: 5-methyl-tetragidrofoliye-vuyu (5-CH3-H4-folic), 5,10-me-tilen-tetragi drofoliyevy (5,10-CH2-H4-folic), 5,10-metilidin-
tetrahydrofolic (5,10-SN-H4-folic), 10-formiltetragidrofo-
liyevy (10-sales tax-H4-folic), 5-folinic
(5-Sales tax-H4-folic) and 5-formimino-tetrahydrofolic (5-CH-NH-H4-folic) to - you. Interconversions of these coenzymatical forms folic to - you form a so-called cycle folic to - you.
Important function of coenzymatical forms F. to. their participation in biosynthesis of purine bases of adenine and a guanine serves. In this process
Yu-sales tax-H4-folic to - that is a source of the 2nd carbon atom of a purine ring, and 5,10-SN-H4-folic acid — a source of the 8th carbon atom of this ring.
FOLIC ACID of 363
V biosynthesis of a pirimidinovy ring coenzymatical forms F. to. directly involved is not, but they act as donors of methyl group at formation of a dezok-citymidinmonofosfat (DTMF) from-zoksiuridinmonofosfata (DUMF). A direct donor of a one-carbon fragment in this reaction is 5D0-CH2-H4-folic acid; 5-CH3-H4-folic acid is a donor of methyl group at synthesis of methionine from Ying's gamocyst.
For definition F. to. and its derivatives in biol. objects, blood serum and fabric extracts widely use mikrobiol. methods, applying as test organisms of Lactobacillus casei of ATCC 7469 (to determination of total amount of folates and their derivatives) and Pediococcus cerevisiae of ATCC 8081, to-rye have selective sensitivity to various forms F. to. also are suitable for their separate definition.
For quantitative definition F. to. widely apply also methods of competitive linkng with use specifically connecting F. to. the proteins secreted from cow's milk or from kidneys of a pig, and commercial sets of such proteins.
For the analysis of pure solutions F. to. flyuorimetrichesky methods are suitable, but at a research biol. material they demand difficult and heavy works on isolation F. to. and its derivatives from the impurity preventing definition. For division of various forms of folic acid which are in mix use methods of a column and thin-layer chromatography (see).
T. to. and its derivatives are eurysynusic in the nature. Full-fledged source F. to. green vegetables and fruit serve. In potatoes contains 8, in cabbage 10 — 31, oranges of 5 mkg folic to - you on 100 g of an edible part of a product. Rather F is a lot of. to. in bread (18 — 32 mkg! 100 g). F is exclusively rich. to. beef liver (240 mkg! 100 g). Meat, eggs and milk are rather poor in F. to.
The recommended norm of consumption F. to. the adult makes 200 mkg a day, at pregnancy and feeding it increases to 600 mkg.
T. to. and its coenzymatical forms as connections are quite unstable therefore they can easily collapse at tekhnol. and culinary processing of food. Especially easily F collapses. to. in vegetables, at long cooking to-rykh loss F. to. can reach 80 — 95%. In meat products F. to. and its derivatives are steadier.
At insufficiency of Folacinum (F. to. and its derivatives) first of all fabrics suffer, for to-rykh intensive synthesis of DNA and high speed of cell fission — the hemopoietic tissue and a mucous membrane of intestines are characteristic. The macrocytic (megaloblastp-chesky) giiyerkhromny anemia morphologically similar to pernicious (B12-scarce) anemia of Addison — Birmera develops (see. Pernicious anemia), developing at disturbance of absorption of B12 vitamin (see Cyanocobalamine). Along with disturbance of an erythrogenesis also function of a white sprout of blood with development of a leukopenia (see) and thrombocytopenia is slowed down (see). At the hypovitaminosis caused by insufficiency of Folacinum reveal stomatitis (see), gastritis (see) and enteritis (see). Deficit of Folacinum during pregnancy can have teratogenic effect, be the cause of prematurity, disturbances of mental development of newborns. Additional preventive reception F. to. it is necessary for pregnant women and the feeding women, at to-rykh insufficiency of Folacinum meets quite often as well as at premature children and elderly people. Low consumption of animal products and fresh vegetables, and also high thermolability F can be one of the reasons of insufficiency of Folacinum. to. and its derivatives, leading to considerable losses of this vitamin at thermal treatment of foodstuff. At pregnant women insufficiency of Folacinum can often be combined with deficit of iron. Also disturbances of its absorption can be the cause of insufficiency of Folacinum at hron. coloenterites and after enterectomies, and also long reception of the barbiturates oppressing utilization F. to. and its derivatives in an organism, hron. alcoholism, the deficit of B12 vitamin breaking exchange of coenzymatical forms F. to., reception of pharmaceuticals, being antagonists F. to., napr, sulfanamide drugs, Chloridinum (see) etc., suppressing ability to use paraaminobenzoic to - that for biosynthesis F at microorganisms of intestinal microflora. to.
About security of the person with Folacinum it is possible to judge by concentration of folates in whole blood, blood serum and erythrocytes. Normal the general content of folates in blood serum makes from 6 to 20 ng/ml. According to WHO experts, the content of folates in blood serum lower than 6 ng! the ml can be considered as the testimony of insufficiency of Folacinum.
For assessment of security of an organism with Folacinum use the test for excretion formiminoglutami-new to - you after loading a histidine (see the Histidine). Normal in days it is removed apprx. 35 mg formimino-glutaminic to - you, and at deficit of Folacinum its removal increases up to 400 — 450 mg. In a similar way excretion lessons-ninovoy to - you, being the biosynthetic predecessor for-mimpnoglutaminovy to - you increases at its education from a histidine.
Judge insufficiency of Folacinum also on morfol. to composition of blood, reduction of quantity of erythrocytes, emergence of giiyersegmentirovan-ny multinuclear leukocytes. At a combination of insufficiency of Folacinum to deficit of iron the macrocytosis in blood can be absent. Secondary functional insufficiency of Folacinum can develop at deficit of B12 vitamin in this connection disturbances of a hemopoiesis (see) and increase in excretion for-miminoglutaminovy to - you take place both at insufficiency of a fo-latspn, and at insufficiency of Bi2 vitamin. For differentiation of these states it is necessary to investigate concentration of folates and kobat amines in blood serum. As the reliable test for differential diagnosis of deficit of Folacinum and Bi2 vitamin serves excretion with urine of methyl-malonic acid, edges does not depend on security of an organism with Folacinum and increases only at a lack of B12 vitamin.
Folic acid as drug.
In medicine folic acid (Acidum folicum; synonym: vitamin of AF,
pteroilglutaminovy to - that, Folacid, Folacin, Folic Acid, etc.) it is used as medicine. For prevention of the insufficiency of Folacinum connected with unsatisfactory or unbalanced food about 25 — 50 mkg of drug daily are recommended to accept; during pregnancy — on 400 mkg, during the feeding by a breast — on 300 mkg a day.
With to lay down. purposes F. to. apply to stimulation of an erythrogenesis in initial stages of macrocytic anemia of an alimentary origin and megaloblastichesky anemia at pregnancy. At a spra drug reduces or eliminates a wedge, displays of a disease, normalizes a hemopoiesis; at the same time it is necessary to appoint cyanocobalamine, ascorbic acid (see), drugs of a crude liver, an autohemotherapy (see). Besides, F. to. apply to treatment of the anemias and a leukopenia caused by reception of nek-ry pharmaceuticals or ionizing radiation and also at the anemias arising after a resection of a stomach and intestines at alimentary anemias of newborns. Due to the beneficial effect F. to. to functional activity of intestines drug is appointed as a part of complex therapy at hron. gastroenteritis and tuberculosis of intestines. At treatment of pernicious anemia F. to. it is necessary to apply surely together with ascorbic to - that and cyanocobalamine.
Appoint F. to. inside. With to lay down. the purposes usually adult recommend to accept 0,005 g (5 mg) a day, to children — in smaller doses depending on age. Duration of a course of treatment is 20 — 30 days.
Form of release: powder, tablets on 0,001 g. Also the tablets containing folic to - that (0,005 g) and ascorbic to - that (0,1 g), and the tablets containing folic to - that (0,005 g) and cyanocobalamine (0,00005 g) are issued. Store in the dark place in banks from orange glass.
Coenzymatical drug F. to. — leykovorin apply to correction of side effect of a methotrexate (Amethopterinum) — an antimetabolite F. to. — at treatment of malignant new growths by it. Bibliography: Vitamins, under the editorship of M. I. Smirnov, M., 1974; Halmuradov A. G., Totsky V. N. and Chagovets R. V. Membrane transport of coenzymatical vitamins and coenzymes, page 165, Kiev, 1982; Experimental vitaminology, under the editorship of Yu. M. Ostrovsky, page 345, Minsk, 1979; The vitamins, Chemistry, physiology, pathology, methods, ed. by W. H. Sebrell a. R. S. Harris, v. 4, N. Y. — L., 1967; Vitamins and coenzymes, ed.
by D. B. McCormick a., L. D. Wright, N. Y. a. o., 1979.
V. B. Spirichev; V. M. Avakumov (pharm.).