BILE ACIDS (synonym trihydroxycholanic acids) — the organic acids which are specific components of bile and playing an important role in digestion and absorption of fats, and also in some other processes happening in digestive tract including in transfer of lipids in an aqueous medium. to. represent also end product of exchange cholesterol (see) which is brought out of an organism generally in a look. to.
By the chemical nature. to. are derivatives cholanic to - you (C 23 H 39 COOH), to ring structure a cut attached one, two or three hydroxylic groups. Side chain. to., as well as in a molecule cholanic to - you, include 5 carbon atoms with COOH group on the end.
Contain in bile of the person: cholic (3-альфа,7-альфа,12-альфа-триокси-5-бета-холановая) to - that:
chenodesoxycholic (anthropodeoxycholic) (3 alpha, 7 - alpha dioxy - 5 - beta cholanic) to - that:
and deoxycholic (3 alpha, 12 - alpha dioxy - 5 - beta cholanic) to - that:
besides, or in the form of traces contain in trace amounts lithocholic (Z - alpha monooxy - 5 - beta cholanic), and also allocholic and ursodezoksikholevy to - you — stereoisomers cholic and chenodesoxycholic to - t. In total. to. are present in bile (see) in the conjugated look. A part them is conjugated with glycine (glycine) in glycocholic or glycochenodesoxycholic to - that, and a part — with taurine in taurocholic:
or taurokhenodezoksikholevy to - that. In hepatic bile Zh. to. dissociate and are in a form of zhelchnokisly sodium salts and potassium (dressing gowns and dezoksikholat of Na and To) that is explained by alkaline pH values of bile (7,5 — 8,5).
From all. to. only cholic and chenodesoxycholic to - you are initially formed in a liver (them call primary) whereas others are formed in intestines under the influence of enzymes of intestinal microflora and carry the name of secondary. They are soaked up in blood and then again cosecrete liver as a part of bile.
At the amicrobic animals who are grown up in sterile conditions are only present at bile cholic and chenodesoxycholic to - you, and deoxycholic and lithocholic are absent and appear in bile only with entering into intestines of microorganisms. It confirms secondary education of these. to. in intestines under the influence of microflora from cholic and chenodesoxycholic to - t respectively.
Primary. to. are formed in a liver of cholesterol.
This process is quite difficult since. to. differ from cholesterol on a stereochemical configuration of two sites of a molecule. Hydroxylic group at the 3rd C-atom in a molecule Zh. to. is in alpha situation, an in a molecule of cholesterol — in beta situation. Hydrogen at the 3rd C-atom Zh. to. is in p-situation that corresponds to trans-configuration of rings And yes In, and in cholesterol — in a-situation (cis configuration of rings And yes In). Besides. to. support the bigger number of hydroxylic groups, shorter side chain which is characterized by existence of a carboxyl group.
Process of transformation of cholesterol in cholic to - that begins with a hydroxylation of cholesterol in 7alfa-situation, i.e. with inclusion of hydroxylic group in situation 7, then oxidation of OH group at the 3rd S-atom in ketogroup, movement of a double bond from the 5th S-atom to the 4th C-atom, a hydroxylation in 12 - alpha situation etc. follows. All these reactions are catalyzed by microsomal enzymes of a liver at presence OVER • H or NADF • H. Oxidation of a side chain in a molecule of cholesterol is carried out with the participation of a number of dehydrogenases in the presence of ATP, KOA and ions of Mg 2+ . Process goes through a mode of formation 3 alpha, 7 alpha, 12 - alpha trioksikoprostanovoy to - you, edges then is exposed to beta oxidation. In a closing stage the three-carbon fragment representing a propionil-Co separates, and the side chain of a molecule, thus, is shortened. The sequence of these reactions in some links can change. E.g., education of ketogroup in 3 - beta situation can happen not to, and after a hydroxylation in 12 - alpha situation. However it does not change the main direction of process.
Process of education chenodesoxycholic to - you from cholesterol have some features. In particular, oxidation of a side chain with formation of a hydroxyl at the 26th S-atom can begin at each stage of process, and the hydroxylated product participates further in reactions in the usual sequence. It is possible that early joining of OH group to the 26th C-atom in comparison with the usual course of process is an important factor in regulation of synthesis chenodesoxycholic to - you. It is established that this to - that is not a predecessor cholic and does not turn into it; similarly and cholic to - that in a human body and animals does not turn into chenodesoxycholic.
Konjyugirovaniye Zh. to. proceeds in two stages. The first stage consists in education atsil-KOA, i.e. KOA-ethers Zh. to. For primary. to. this stage is carried out already at a final stage of their education. Second stage of a konjyugirovaniye. to. — actually Konjyugirovany — consists in connection by means of an amide link of a molecule Zh. to. with glycine or taurine. This process is catalyzed by lizosomalny acyltransferase.
In bile of the person the main. to. — cholic, chenodesoxycholic and deoxycholic — are in a quantitative ratio 1:1:0,6; glycine and taurinovy conjugates of these to - t — in the ratio 3:1. The ratio between two of these conjugates changes depending on character of food: in case of dominance of carbohydrates in it abundance of glycine conjugates increases, and at a high-protein diet — taurinovy conjugates. Corticosteroid hormones increase abundance of taurinovy conjugates in bile. On the contrary, at the diseases which are followed by proteinaceous insufficiency the share of glycine conjugates increases.
The relation glycine - conjugated to taurine - conjugated. to. at the person changes under the influence of thyroid hormone, increasing at hypothyroid a state. Besides, at patients with a hypothyroidism cholic to - that has bigger time of semi-existence and more slowly exchanges, than at patients with a hyper thyroidism that is followed by increase in content of cholesterol in blood at patients with the lowered function of a thyroid gland.
At animals and the person at castration the content of cholesterol in blood increases. In an experiment decrease in concentration of cholesterol in blood serum and increase in education. to. observed at administration of estrogen. Nevertheless effect of hormones on biosynthesis. to. is studied not enough.
In bile of various animals structure. to. strongly varies. Are found in many of them. to., absent at the person. So, at some amphibians the main component of bile is kiprinol — bilious alcohol which, unlike cholic to - you, have longer side chain with two hydroxylic groups at the 26th and 27th S-atoms. This alcohol is conjugated preferential with sulfate. At other amphibians bilious alcohol bufol prevails, having IT is groups at the 25th and 26th C-atoms. At a pig is present at bile hyocholic to - that with OH группойв the provision of the 6th S-atom (3 alpha, 6 alpha, 7 - alpha trioksikholanovaya to - that). Are available for rats and mice alpha and beta marikholevye to - you — stereoisomers hyocholic to - you. At the animals eating vegetable food in bile prevails chenodesoxycholic to - that. E.g., at a Guinea pig it is only of the main. to. Cholic to - that, on the contrary, is more characteristic of carnivores.
One of the main functions Zh. to. — transfer of lipids in an aqueous medium — it is connected with their detergentny properties, i.e. with their ability to dissolve lipids by formation of micellar solution. These properties Zh. to. are shown already in tissue of a liver where with their participation the micelles which received the name of a lipidic complex of bile are formed of a number of components of bile (or finally form). Thanks to inclusion in this complex the lipids cosecreted by a liver and some other low solubility substances in water are transferred to intestines in the form of homogeneous solution as a part of bile.
In intestines of salt Zh. to. participate in emulsification of fat. They are a part of the emulsifying system including a saturated monoglyceride, unsaturated fat to - that and salts Zh. to. At the same time they play a role of stabilizers of a fatty emulsion. to. carry out also important role as a peculiar activator of pancreatic lipases (see). Their activating influence is expressed in the shift of an optimum of action of a lipase which at presence. to. moves with pH 8,0 to pH 6,0, i.e. up to that size pH, edges it is more constantly supported in a duodenum during digestion of greasy food.
After a lipolysis a lipase products of this splitting — monoglycerides and fatty acids (see) form micellar solution. A crucial role in this process is played by salts Zh. to. Thanking their detergent noma to action in intestines steady micelles in an aqueous medium are formed (see. Molecule ), the containing cleavage products of fat, cholesterol and often phospholipids. In such look these substances are transferred from emulsion particles, i.e. from the place of hydrolysis of lipids, to the soaking-up surface of an intestinal epithelium. In the form of the micellar solution which is formed with the participation of salts Zh. to., are transferred in went. - kish. path and fat-soluble vitamins. Switching off. to. from digestive processes, napr, at experimental removal of bile from intestines, leads to decrease in absorption of fat in went. - kish. a path for 50% and to disturbance of absorption of fat-soluble vitamins up to development of the phenomena of a vitamin deficiency, napr, insufficiency of phthiocol. In addition. to. have a promoting effect on growth and functions of normal intestinal microflora: at the termination of intake of bile in intestines life activity of microflora undergoes essential changes.
Having executed the fiziol, a role in intestines. to. in overwhelming quantity are soaked up in blood, are returned to a liver and again cosecrete as a part of bile. There is, thus, a continuous circulation. to. between a liver and intestines. This process is called hepatoenteric (enterogepatichesky or portal and biliary) circulation. to.
Ground mass. to. it is soaked up in the conjugated look in an ileal gut. In a proximal part of a small bowel a nek-swarm quantity. to. passes into blood by passive absorption.
The researches conducted by means of marked 14 C. to., showed that bile contains only small part Zh. to., again synthesized by a liver [S. Bergstr, H. Danielsson, 1968]. Only 10 — 15% of total quantity fall to their share. to. Main weight. to. bile (85 — 90%) make. to., reabsorbirovanny in intestines and repeatedly cosecreted as a part of bile, i.e. to., participating in hepatoenteric circulation. Common pool. to. at the person averages 2,8 — 3,5 g, and they make 5 — 6 turns per day. At the different animals range of speeds made. to. per day, strongly varies: at a dog it is also equal 5 — 6, and at a rat 10 — 12.
Part Zh. to. is exposed in intestines to a dekonjyugirovaniye under the influence of normal intestinal microflora. At this nek-swarm the quantity loses them hydroxylic group, turning in deoxycholic, lithocholic or into others to - you. All of them are soaked up and after a konjyugirovaniye in a liver cosecrete as a part of bile. However 10 — 15% all come to intestines. to. after a dekonjyugirovaniye is exposed to deeper degradation. As a result of the processes of oxidation and recovery caused by enzymes of microflora, these. to. undergo various changes which are followed by a partial rupture of their ring structure. A number of the formed products then is allocated with excrements.
Biosynthesis. to. it is controlled as a negative feed-back by a certain quantity. to., returned to a liver in the course of hepatoenteric circulation.
It is shown that different. to. render qualitatively and quantitatively various regulating action. At the person, e.g., chenodesoxycholic to - that slows down education cholic to - you.
Increase in content of cholesterol in food leads to strengthening of biosynthesis. to.
Destruction and emission of part Zh. to, represent the most important way of excretion of end products of exchange of cholesterol. It is shown that at the amicrobic animals deprived of intestinal microflora range of speeds, made is reduced. to. between a liver and intestines, and excretion sharply decreases. to. with excrements that is followed by increase in content of cholesterol in blood serum.
Thus, rather intensive secretion. to. as a part of bile and their turning into intestines under the influence of microflora are extremely important both for digestion, and for exchange of cholesterol.
Normal in urine at the person Zh. to. do not contain, their very small amounts appear in urine at obturatsionny jaundice (early stages) and acute pancreatitis. to. are the strongest choleretics, napr, dehydrocholic acid (see). This property Zh. to. it is used for their introduction to structure cholagogue means (see) — a dekholina, Allocholum, etc. to. stimulate a peristaltics of intestines. The locks observed at patients with jaundice can be caused by deficit of dressing gowns (salts Zh. to.). However single-step receipt of a large number konts. bile in intestines, and with it and a large number. to., observed at a number of patients after removal of a gall bladder, can cause a diarrhea. Besides. to. possess bacteriostatic action.
General concentration. to. in blood and their ratio significantly change at a number of diseases of a liver and gall bladder that is used in the diagnostic purposes. At parenchymatous damages of a liver ability of hepatic cells to take sharply decreases. to. from blood therefore they collect in blood and are allocated with urine. Strengthening. to. in blood it is observed also at difficulty of outflow of bile, especially at obturation of the general bilious channel (a stone, a tumor) that is followed also by disturbance of hepatoenteric circulation with sharp reduction or disappearance of conjugates of dezoksikholat from bile. Long and essential strengthening. to. in blood can have the damaging effect on hepatic cells with development of necroses and change of activity of some enzymes in blood serum.
High concentration of dressing gowns in blood causes bradycardia and hypotonia, a skin itch, hemolysis, increase in osmotic resistance of erythrocytes, breaks processes of a blood coagulation, slows down a blood sedimentation rate. With allocation at diseases of a liver. to. through kidneys connect development of a renal failure.
At acute and hron, cholecystitises reduction of concentration or total disappearance of dressing gowns from vesical bile is observed that is explained by reduction of their education in a liver and acceleration of absorption by their mucous membrane of the inflamed gall bladder.
. to. and their derivatives destroy within several minutes of a blood cell including leukocytes that should be considered at assessment of diagnostic value of quantity of leukocytes in duodenal contents. Holata destroy as well the fabrics which are not adjoining in fiziol, conditions to bile cause increase in permeability of membranes and a local inflammation. At hit of bile, e.g., heavy peritonitis quickly develops in an abdominal cavity. In the mechanism of development of acute pancreatitis, antral gastritis and even stomach ulcer a certain part is assigned. to. The possibility of injury of the most gall bladder konts is allowed. the bile containing a large number. to. («chemical» cholecystitis).
. to. are an initial product for production of steroid hormones. Thanks to similarity of chemical constitution of steroid hormones and. to. the last possess the expressed antiinflammatory action. On this property Zh. to. the method of treatment of arthritises by topical administration konts is based. bile (see. Bile ).
For treatment of the ponos arising after operational removal of a part of intestines, and a persistent skin itch at patients with diseases of a liver and bilious ways the drugs connecting are used. to. in intestines, napr, holestiramin.
Bibliography: Mosquitoes F. I. and Ivanov A. I. Bile acids, a physiological role, clinical value, Rubbed. arkh., t. 44, No. 3, page 10, 1972; Kuvayeva I. B. Metabolism and intestinal microflora, M., 1976, bibliogr.; Saratikov A. S. Bile production and cholagogue means, Tomsk, 1962; Achievements of hepathology, under the editorship of E. M. Tareeva and A. F. Blyugera, century 4, page 141, Riga, 1973, bibliogr.; Bergstrom S. Danielsson H. Formation and metabolisme of bile acids, Handb. Physiol., sect. 6, ed. by G. F. Code, p. 2391, Washington, 1968; The bile acids, chemistry, physiology and metabolism, ed. by P. P. Nair a. D. Kri-tshevsky, v. 1—2, N. Y., 1973, bibliogr.; Borgstrom B. Bile salts, Acta med. scand., v. 196, p. 1, 1974, bibliogr.; D a-nielsson H. S j o v a 1 1 J. Bile acid metabolism, Ann. Rev. Biochem., v. 44, p. 233, 1975, bibliogr.; Hanson R. F. a. o. Formation of bile acids in man, Biochim, biophys. Acta (Amst.), v. 431, p. 335, 1976; S h 1 at g i n G. K. Physiology of intestinal digestion, Progr, food Nutr., y. 2, p. 249, 1977, bibliogr.
G. K. Shlygin; F. I. Komarov (wedge.).