THIAMIN (synonym: vitamin B 1 ustar. thiamin) — one of the most important water-soluble vitamins of group B; 4-метил-5β-оксиэтил-N-(the 2nd '-methyl-4 '-amino-5 '-metenilpirimidin) - tiazoliya.
Biol. value T. it is caused by action of its derivative — a tiamindifosfata (TDF; thiamine pyrophosphate, cocarboxylase), formed of thiamin and ATP with the participation of enzyme of a tiaminkinaza (KF 184.108.40.206). Tiamindifosfat is a coenzyme (see. Coenzymes ) a number of the enzymes playing an essential role in carbohydrate metabolism (see) — pyruvatedehydrogenases (KF 220.127.116.11), alpha ketoglutaratdegidrogenazy (oksoglutaratdegidrogenaza; KF 18.104.22.168), transketomanholes (KF 22.214.171.124) and dehydrogenases of ketonic acids with a branched side chain. Lack of T. in a human body and animals leads to disturbance of oxidation of carbohydrates, braking of the processes of power and plastic providing vital signs depending on TDF, accumulation in blood and fabrics of nedookisleniy metabolic products that, in turn, brings to patofiziol. and patomorfol. to the changes creating a picture of a hypovitaminosis (see. Vitamin deficiency ), one of forms to-rogo is beriberi (see).
T. it is eurysynusic in wildlife. It is present at microorganisms, plants and all fabrics of an animal organism. Yeast and wheaten germs are especially rich with it. T. it is synthesized by plants and many microorganisms. In a human body and the highest animal T. it is not synthesized therefore they shall receive it with food. Need of the person for T. makes 0,6 mg on 1000 kcal of a daily diet or from 1.5 to 2,4 mg a day depending on energy costs.
T are richest. bread, bakery products (see) from coarse flour or fortified flour, grain (see. Grain products ), especially buckwheat, oat, millet, bean products (see), liver, low-fat pork. Milk and dairy products the same as the majority of vegetables, are poor in thiamin (tab).
Usual thermal culinary treatment influences the maintenance of T a little., but heating in alkaline condition conducts to a considerable inactivation of vitamin. Large numbers of T. are lost with bran at preparation of high-grade flour in this connection vitaminization of high-grade flour by addition in it in the course of its production of T practices. together with Riboflavinum (see) and niacin (see) to the level corresponding to their content in initial grain (see. Vitaminization of foodstuff ).
In live organisms of T. is present not only in the form of TDF. but also in the form of free T. and two other its phosphoric ethers — a tiaminmonofosfat (TMF) and a tiamintrifosfat (TTF). Falls to the share of TDF apprx. 60 — 80% of only A T., the person who is contained in an organizkhma. At plants and microorganisms of TDF participates in a catalysis of reactions of not oxidizing decarboxylations (see) alpha ketonic acids.
T. there is usually in the form of salts, one of to-rykh — tiaminkhlorid (C 12 H 17 ON 4 SCI-HCl, pier. weight 337,27) crystallizes with 1/2 H 2 O in the form of colourless monoclinical needles with t°gk 233 — 244 ° and 250 — 252 ° (with decomposition). Are known also tiaminbromid (C 12 H 17 ON 4 SBrHBr-0,5H 2 O, pier. weight 435,19, t°pl 220 ° and 229 — 231 °) and tiaminmononitrat (C 12 H 17 ON 4 SNO 3 , pier. weight 327,37, t°pl 164 — 165 ° and 196-200 °). Salts T. well than a rastvorima in water, it is slightly worse in alcohols, are not ether-soluble, chloroform, benzene and acetone. Absorption spectrum of T. in an aqueous medium at pH 7,0 has two maxima (at 233 — 235 and 265 — 267 nanometers), and in acid medium — one maximum (at 245 — 247 nanometers). T. it is steady against heating and action of oxidizers in acid medium; in alkaline condition easily is oxidized in a thiochrome — substance of yellow color with t°pl 227 ° (with decomposition), possessing in this environment intensive blue fluorescence with a maximum of radiation at 460 — 470 nanometers.
In the industry of T. receive condensation 2-methyl-4-amino-5-aminometenilpirimidina, carbon sulfur and 5-chlorine-5-oxypentanona-2, and TDF — interaction of T. and pyrophosphoric to - you.
Participation of T. in a metabolism is defined by the TDF coenzymatical function and that role, to-ruyu in metabolism play TDF-zavisimye enzymes.
TDF-zavisimaya the pyruvatedehydrogenase takes part in oxidizing decarboxylation pyroracemic to - you with education atsetil-KOA, providing a possibility of full oxidation of carbohydrates (see) and utilization of the energy concluded in them. As a result of this transformation pyroracemic to - that, formed at glycolysis (see) from glucose (see), joins in a cycle tricarboxylic to - t (see. Tricarboxylic acids cycle ). Formed during this enzymatic process atsetil-KOA serves as the donor of the rest acetic to - you (so-called active acetate), used for biosynthesis of the major connections — fatty acids (see), sterols (see), including. cholesterol (see), steroid hormones (see), and also bile acids (see) and acetylcholine (see).
Another TDF-zavisimy enzyme — alpha ketoglutaratdegidrogenaza participates in oxidizing decarboxylation alpha and keto-glutaric to - you with education amber to - you (succinate). This transformation is an important stage of a cycle tricarboxylic to - t. Besides, TDF takes part in oxidizing decarboxylation of ketonic acids with a branched carbon chain — alpha and ketoisovalerianic, alpha ketometnlvalerianovoy and alpha and ketoisokapron, being products of deamination (see) valine (see), isoleucine (see) and leucine (see). Reaction plays an essential role in processes of a catabolism of proteins, providing oxidation and utilization of these amino acids.
TDF-zavisimaya a transketomanhole is one of enzymes of a pentozofosfatny way of oxidation of carbohydrates — the pentozny cycle (see. Carbohydrate metabolism) which is the main source to NADF-N (see. Nicotinamide adenine dinucleotide ) and ribozo-5-phosphate, from to-rykh the first it is used as hydrogen donator in numerous recovery biosynthetic processes, and the second is a part of nucleotides and nucleic acids (see).
T. in the form of TDF is directly involved in implementation of the catalytic act thanks to the ability to dissociate with eliminating of a proton at the second carbon atom of a tiazolovy ring then T. acquires structure of a highly active bipolar ion, to-ry interacts with a molecule of the turned substrate.
At insufficiency of T. the most considerable patol. changes develop in digestive, nervous and cardiovascular systems. Characteristic displays of hypovitaminosis of Vkh are the general weakness, a lose of weight of a body up to a cachexia. Disturbances from outside went. - kish. a path are among the earliest manifestations of insufficiency of T. also are expressed in loss of appetite, nausea, decrease in gastric secretion, an achlorhydria, atony, locks.
Disturbances from a nervous system are shown by headaches, weakness, bystry fatigue, irritability, easing of memory, defeat of peripheral nerves. Muscular weakness, morbidity of gastrocnemius muscles at a palpation are characteristic, loss of a muscle tone, paresthesia and hyperesthesia, polyneurites, fading of tendon jerks, atrophic paralyzes of muscles of extremities, spasms. The severe form of a hypovitaminosis is the cornerstone of the alcoholic encephalopathies (see) which are often caused hron. alcoholism and the movements which are followed by a lack of coordination, an ophthalmoplegia, confusion of consciousness.
Histologically at heavy insufficiency of T. find dystrophic changes in distal departments of peripheral neurons with disintegration of myelin substance and vacuolation neuro lemmotsshyuv (schwannian cells). Patomorfol. the changes in gray matter of a brain localized preferential around ventricles have an appearance of focal hemorrhages with proliferation of cells of an endothelium of blood vessels and cells of a neuroglia.
Patol. the changes in cardiovascular system connected with disorder of the central regulation of a vascular tone and disbolism are shown by tachycardia, pains in heart, decrease in the ABP, expansion of borders of heart (preferential its right departments). In very hard cases heart failure with cyanosis, developments of stagnation in a liver, hypostases develop. Expressiveness of symptoms of a hypovitaminosis of B1 depends on degree of insufficiency of thiamin in an organism.
Insufficiency of oryzamin sometimes develops at uniform food the purified rice, products from fine flour, etc. Elderly people have a lack of T., as well as some other vitamins (see), it can be caused by the general decrease in amount of the consumed food and reduction of absorption of polyneuramins intestines. Reason of a lack of T. also disturbance of absorption of vitamins can serve in an organism at hron. diseases of intestines: enterita, coloenterites, etc. In these cases deficit of T. it is, as a rule, combined with deficit of other vitamins (polyhypovitaminosis). Lack of T. it can be also caused by excess consumption of the products containing thiaminase (see), the destroying T. (e.g., crude fish), or development in went. - kish. path of pathogenic microflora (you. thiaminolyticus, you. aneurinolyticus), producing this enzyme.
Along with insufficiency of T. an alimentary origin the diseases caused by genetic defects of exchange of T are known. and TDF-zavisimykh enzymes (see. Enzymopathies ). These diseases clinically similar to displays of hypovitaminosis of B1 note at sufficient receipt of T. in an organism. Treat them the subacute necrotic infantile encephalomyelopathy for the first time described by D. J. Leigh, at a cut in tissue of a brain formation of TTF as a result of genetically caused insufficiency of enzyme of a tiamindifosfatkinaza (KF 126.96.36.199) is broken; the vestibulomozzhechkovy periodic ataxy caused by inborn defect of a piruvatdegidrogenazny complex; tiaminzavisimy megaloblastichesky anemia (see. Anemia ) and the tiaminzavisimy form of dekarboksilazny insufficiency (see), at a cut urine has a smell of maple syrup.
For assessment of security of a human body of T. widely use definition of its daily excretion with urine. This indicator well reflects receipt of T. with food; at sufficient intake of polyneuramin an organism it usually exceeds 100 mkg. At impossibility of collecting daily urine it is possible to define the maintenance of T. in an hour portion, i.e. in the urine collected on an empty stomach in 1 hour after bladder emptying; the maintenance of T is normal. there have to be not less than 15 mkg. Besides, in this case excretion of T. it is possible to correlate to excretion of creatinine (see. Creatine ). At sufficient receipt of T. with food this indicator shall not be lower than 65 mkg of T. on 1 g of creatinine.
Maintenance of T. in urine usually determine flyuorimetrichesk (see Flyuorimetriya) by a method Vanga — Harris after oxidation of thiamin to a thiochrome by means of red blood salt (ferricyanide of potassium).
For assessment of a saturation of an organism of T. investigate its content in whole blood or erythrocytes. The general maintenance of T is normal. in blood makes 6 — 12 mkg / 100 ml, decreasing at deficit of B1 vitamin to 2 — 4 mkg / 100 ml and below. T. is present preferential at uniform elements of blood whereas its concentration in a blood plasma is very small. Keeping of the general T. in blood define flyuorimetrichesk after preliminary splitting of TDF with the help phosphatases (see), to-rykh fermental drug from Aspergillus niger or Aspergillus oryzae can be a source (orizin). In the tests which are not processed by phosphatases determine content free by T., and a difference between the general and to free T. gives the maintenance of its fosfo-rilirovanny forms, hl. obr. TDF. The maintenance of TDF in blood and fabrics can be determined by also enzymatic method with an apoenzyme of a pyruvatedecarboxylase of yeast.
Specific functional test of security of an organism of T. definition in a hemolysate of blood of activity TDF-zavisimogo of enzyme transketomanholes is, edges considerably decreases already at early stages of a hypovitaminosis of B1 (lower than 15 — 20 µmol of sedogeptulozo-7-phosphate in 1 ml at 1 o'clock) that is caused by shortage of its coenzyme — TDF. Addition of TDF to a hemolysate of blood in this case activates to a transketomanhole. Extent of such activation, or TDF-effect, serves as a measure of security of an organism of T. Normal this size does not exceed 15%, at a hypovitaminosis of B1 makes 15 — 25%, at clinically expressed avitaminosis of B1 reaches 30% and more.
Functional test of security of an organism of T. also determination of content in blood and urine is pyroracemic to - you, the quantity a cut increases at deficit of T. owing to blocking TDF-zavisimogo of oxidizing decarboxylation of this to - you. However such indicator is less specific since pyroracemic to - that can collect in an organism and in other conditions, in particular at a fabric hypoxia.
Thiamin as drug
Thiamine as drug (Thiaminum, Vitaminum B 1 ; synonym: Aneurin, Anevryl, Betaneurin, Betavitan, Oryzanin, Vitaplex B1, etc.). As medicinal prophylactics in medicine apply Thiamini bromidum, Thiamini chloridum, phosphothiamin, Benphothiaminum and a coenzymatical form of B1 vitamin — Cocarboxylasi hydrochloridum.
The main pharmakol. properties of drugs are caused by their specific participation in tiaminzavisimy metabolic processes, disturbance to-rykh happens or at a hypovitaminosis of W and genetically caused disturbances of exchange, or for the second time at nek-ry patol. processes. T. exerts impact on carrying out nervous impulses in neuromuscular synapses, has ganglioblokiruyushchy and kurarepodobny properties, anticonvulsant activity, positively influences functional activity of cardiovascular system. In an experiment it is revealed that the most expressed side effect Thiamini bromidum, a little smaller — thiamin a hydrochloride, smaller — phosphothiamin and Benphothiaminum possesses.
Thiamini chloridum or Thiamini bromidum, getting into intestines in the form of free T., are affected by enzyme of a thiaminase, to-ry partially the most part of T destroys by T. Odnako. it is soaked up in blood; then T. in tissue of a liver, kidneys, hearts, a brain, etc. TDF is phosphorylated with formation of its phosphoric ethers, especially. At high concentration of T. it is removed by kidneys in not changed look or in the form of products of its disintegration.
Advantage of phosphothiamin (TMF) before Thiamini chloridum or Thiamini bromidum consists that it represents an intermediate product in the course of transformation of T. into its coenzymatical form and much quicker turns into TDF. Unlike TDF phosphothiamin is capable to get through membranes of cells of an intestinal wall, without being exposed at the same time to dephosphorylation; in medical practice it is applied in the form of tablets. Phosphothiamin has ability to be deposited in body tissues in bigger quantity, than other drugs T.
Benphothiaminum (benzylthiamin-au-monophosphate) on pharmakol. to properties it is close to Thiamini chloridum, but has before it a number of advantages: its side effect is less expressed, it is better soaked up in intestines, is steadier against action of a thiaminase of intestinal microflora and is capable to support longer time in blood the increased concentration of free thiamin.
Drugs T. (except cocarboxylase) apply to prevention or treatment of a hypovitaminosis of B1, and also at neuritis, radiculitis, neuralgia, a flaccid paralysis, a peptic ulcer of a stomach and duodenum, an atony of intestines, hron. to an alkogolizkhma, hron. circulatory unefficiencies and a myocardial dystrophy, a spasm of peripheral vessels, nek-ry diseases of a liver, in Dermatolum. to practice — in complex treatment of a dermatosis of a neurotrophic origin.
Sometimes drugs T. (especially Thiamini chloridum and Thiamini bromidum) allergic reactions (a Quincke's edema, an itch, urticaria) can cause; at intravenous administration intensity of allergic reactions can increase up to development of an acute anaphylaxis (see). Especially carefully it is necessary to appoint drugs T. to persons with burdened and l lergo the logical anamnesis, to women in nredklimakterichesky both a climacteric and to the persons suffering hron. alcoholism.
Contraindications to use of drugs T. allergic diseases and medicinal intolerance serve in the anamnesis. Simultaneous parenteral administration of drugs T is not recommended. with a pyridoxine (see) and cyanocobalamine (see) since the first complicates transformation of T. in biologically active coenzymatical form, and the second strengthens allergenic action
of T. Hranyat drugs T. in hermetically or densely corked container, in the place protected from light.
Benphothiaminum — white crystal powder with a slight smell. Indications to use the same, as for all drugs T.; besides, Benphothiaminum is appointed at atherosclerosis, coronary heart disease at persons of advanced and senile age, at a rheumatic carditis.
A daily dose of 0,1 — 0,2 g (in 1 — 4 reception, after food), a course of treatment of 15 — 40 days. For elderly people the dose is reduced to 0,075 g, for persons of senile age — to 0,05 g a day; course of treatment of 15 — 30 days. At a dermatosis a daily dose of 0,1 — 0,15 g, a course of treatment of 30 — 40 days. At diseases of a liver a daily dose to 0,1 g, a course of treatment of 15 — 30 days.
Form of release: tablets on 0,005 and 0,025 g.
Cocarboxylase (Cocarboxylasum; synonym: thiamine pyrophosphate, Cocarboxylase, Diphosphothiamin, etc.) — white crystal powder of bitterish and acid taste with a slight specific smell. Let's easily dissolve in water, it is insoluble in alcohol, during the heating decays; solutions with concentration of cocarboxylase of 2,5% have pH 1,4 — 1,7. Solutions of cocarboxylase prepare ex tempore. For the medical purposes use Cocarboxylasi hydrochloridum (Cocarboxylasi hydrochlo-ridum).
To treatment of a hypovitaminosis of B1 the kokarboksplaza is not applied. As indications to its appointment serve diabetogenic acidosis, a liver and renal failure, a respiratory acidosis at hron. pulmonary heart, diabetic and hepatic coma, insufficiency of coronary circulation, neuritis, insufficiency of carbohydrate metabolism of a different etiology.
Cocarboxylase usually is a component of complex therapy. Administer the drug intramusculary, subcutaneously or intravenously. A dose for adult 0,05 — 0,1 g, for children of 0,025 — 0,05 g once a day.
Form of release: ampoules on 0,05 g of the lyophilized powder, the ampoule from 2 ml of solvent is applied to everyone. Store in the cool place.
Thiamini bromidum and Thiamini chloridum (Thiamini cbloridum) — white crystal powders with a specific smell of yeast. Easily rastvorima in water, will sterilize solution (pH 2,7 — 3,6) at 100 ° within 30 min. Appoint the adult at initial symptoms of hypovitaminosis In, on 0,005 — 0,01. in day; at later stages of a hypovitaminosis, and also at diseases went. - kish. a path, skin and a nervous system the dose is increased to 0,05 g a day. A course of treatment of adult 30 — 40 days, children — depending on age.
On activity of 1 mg of Thiamini chloridum there correspond 1,29 mg of Thiamini bromidum because of bigger a pier. weight. Parenterally these drugs are used in cases of disturbance of absorbability of T. in intestines or in need of bystry creation of high concentration of B1 vitamin; in blood. Usually adult in days enter intramusculary and about 0,025 — 0,05 g of Thiamini chloridum (1 ml 2,5 pl of 5% of solution) or on 1 ml of 3 or 6% of solution of Thiamini bromidum. Course of treatment of 10 — 30 days.
Hypodermic (sometimes and intramuscular) injections of these drugs are painful in connection with low pH of solutions. In some cases after injections (is more rare at intake) allergic reactions are possible, to-rye can be more expressed at intravenous administration.
Forms of release: Thiamini chloridum — a tablet or a dragee 0,002 of a tablet on 0,005 and 0,01 g, ampoules on 1 ml of 2,5 and 5% of solution; Thiamini bromidum — a tablet or a dragee on 0,00258 g, a tablet on 0,00645 and 0,0129 g, an ampoule on 1 ml of 3 and 6% of solution.
Phosphothiaminum — white, sometimes yellowish powder of acid taste with weak specific to T. smell. Let's easily dissolve in water, it is insoluble in alcohol.
Phosphothiamin is appointed the adult on 0,01 — 0,03 g a day. Indications to use the same, as for other drugs T. At ekstrasistoliya the dose of phosphothiamin is increased to 0,07 g. Course of treatment of 30 — 40 days.
Form of release: tablets on 0,01 and 0,03 g
the CONTENT of THIAMIN IN SOME FOODSTUFF (in mkg on 100 g of a product)
Bibliography: Berezovsky V. M. Chemistry of vitamins, M., 1973; Vitamins, under the editorship of M. I. Smirnov, page 173, M., 1 974; Clinical pharmacology, under the editorship of V. V. Zakusov, page 353, M., 1978; Cocarboxylase and other tiaminfosfata, under the editorship of Yu. M. Ostrovsky, Minsk, 1974; About with t r about in with to and y Yu. M. Active centers and groups in a molecule of thiamin, Minsk, 1975, bibliogr.; With p and r and - h e in V. B. Biochemical bases In ^авитаминоза, in book: Molek. bases of a pas tolite., under the editorship of V. N. Orekhovich, page 22i, M., 1966; With p and r and h e in V. B. and nili Bar e in GO. II. Inborn disturbances of exchange of vitamins, M., 1977; Experimental vitaminology, under the editorship of Yu. M. Ostrovsky, page 176, Minsk, 1979; The vitamins, chemistry, physiology, pathology, methods, ed. by W. H. Sebrell a. R. S. Harris, v. 5, N. Y-, 1972.
V. B. Spirichev; V. M. Avakumov (pharm.).