FIBRINOGEN

From Big Medical Encyclopedia

FIBRINOGEN (fibrin + grech» gennao to create, make; Xing *

the I blood-coagulation factors) — the protein dissolved in a blood plasma, turning under the influence of thrombin into fibrin in the course of a blood coagulation.

In a blood plasma F. contains in concentration from 2 to 4 g/l (depending on the applied methods of definition). Pier. weight (weight) F. much more, than at other proteins of plasma also makes about 340 000. A sedimentation constant of fibrinogen (s20, w) is equal to 7,68. Length of a molecule F. varies to from 42 to 70 them depending on amount of combined water. At ionic strength of native blood a molecule F. as whole it is quite flexible and unstable. In the neutral environment F. has a maximum of absorption in the UF-range at 280 nanometers, at increase in pH to

11.0 maxima of absorption at 282 and 280 nanometers appear.

T. it is dissolved in the diluted salt solutions, drops out in a deposit at cultivation of a blood plasma and it is besieged at increase in ionic strength of solution, i.e. treats fraction of eu-globulins (see Globulins). At constant pH values between

6.0 and 7,0 solubility F. raises with increase in ionic strength of solution. Heating to 50 ° causes a bystry irreversible denaturation and sedimentation F. from solutions. Content of the general nitrogen in fibrinogen makes apprx. 17%, are gray —

1,25%, phosphorus — Nmkg/Sh) mg. A carbohydrate part makes 2,5 — 3% of all molecule F., at the same time from 0,7 to 1,3% fall to the share of hexoses, 0,55 — 1,3% — geksozamin and 0,54 — 0,7% — sialine to - t. Carbohydrate part of a molecule F. N-acetyl-D contacts a proteinaceous part - glyukozaminat - (3 aspartylamide through the rest of asparagine. V F. all known amino acids are found, however threonine, serine, tryptophane, a lysine, glycine, glutaminic and asparaginic to - you prevail. Significant specific differences F are revealed. on a pier. to the weight, primary structure and SOON-and NH2-trailer remains.

Molecule F. represents dimeasures, each subunit to-rogo consists of three types of the ggolipeptidny chains connected by disulfide bridges (SS bonds) in uniform covalent structure. Polipeptid-nye chains are designated by Aa, B(3 and at and have a pier. weight respectively 67 000, 58 000, 47 000; and - and (3 chains on the XH2-ends contain the fibrinopeptides A and B consisting respectively of 16 both 14 amino-acid remains and which are chipped off at effect of thrombin (see) on F. Primary structure is established for Aa-and at - chains and one third (Z-tseii. Between

Bp - and at - the expressed homology is available chains.

Considerable heterogeneity of Ass-polipeptidnykh of chains, as well as molecules F is noted. in general, owing to influence of a pas them thrombin and plaz a mine (see Fibrinolysin) — the main enzymes of a hemostasis (see) both a fibers and zero for (see). In a molecule intact F. there are end products of proteolysis in the form of the large independent functionally important blocks called by domains. The main domains — central (E) about a pier are known. weighing 60 Ltd companies and two peripheral domains (D) about a pier. vesokhm apprx. 95 Ltd companies, there is also a domain the expert. Poly-peptide appreciate three begin in the middle of the central domain. NH2 ends of three chains of one subunit of a molecule F. make a half of the central domain E. These appreciate, proceeding in the peripheral direction, form the domain D, from to-rogo the extensive Aa-tsepi area SOON-kon-tsevaya in the form of the domain the expert departs.

Except a blood plasma and a lymph, T. it is found in thrombocytes. Distinguish extracellular F., the adsorbed on membranes of thrombocytes, and intracellular, connected since Saturday-granu Lamy of thrombocytes (see).

Contents F. in a blood plasma of healthy faces differs in quite big constancy. During the day fluctuations of contents F. in blood are insignificant. During the aging strengthening F is observed. in blood. Despite a high pier. weight F. easily migrates in extravasated space and it is found in a lymph, connecting fabric and intersticial space. At patol. processes quantity extravasated F. can reach 80% of its general contents in an organism. Maintenance of constant quantity F. in a blood channel it is reached as a result of a dynamic equilibrium between the speed of its synthesis, transcapillary exchange and splitting or utilization.

Synthesis F. it is carried out in ribosomes and microsomes of geggatotsit (cells of a parenchyma of a liver). T. it is characterized by high speed of exchange; half-life at the person averages apprx. 3 days.

From 1,5 to 5 g of fibrinogen are daily formed. During the day the liver can update to V3 circulating in blood F. Synthesis F. strengthen adrenokortikotr opny

hormone (see), triiodothyronine (see) and cleavage products F. and fibrin (see). Contains in a blood plasma 75 ± 15% of total quantity F. in an organism. Catabolism F. occurs in a blood plasma, and also in cells of an endothelium of vessels and macrophages; intaktiy F. cells of an endothelium do not take. The fiziol. function F. it is capable to carry out only after transformation under the influence of thrombin into fibrin and the subsequent its spontaneous polymerization. On a nerve a stage thrombin, breaking off in Aa-tsepyakh F. communication between the rest of arginine in the 17th provision of one chain and the rest of glycine in

the 16th provision of other chain, chips off two fibrinoiyeptid And, the representing N-trailer sites on-lipeptidnykh chains, at the second stage thrombin splits communication between the rest of arginine in the 14th situation and the rest of a glutamine in the 15th provision of other chain in In (3 chains and chips off two fibrinoiyeptid of V. Obrazuyushchiyesya after eliminating of fibrinopeptides fibrin-monomers are exposed to polymerization, and then covalent binding under the influence of a fibrinstabiliziruyushchy factor (the XIII factor) of a blood coagulation. T. after turning into fibrin participates in a stop of bleeding from the damaged vessels and processes of a reparation of fabrics, protects from penetration and distribution of a contagium during the healing of wounds. Falloff of contents F. in blood can be the cause of bleeding.

More than 80 cases of inborn deficit F are described. (see Afibri-nogenemiya). Besides, there are hereditary and acquired dysfibrinogenemias connected with change of a structure of a molecule F. in the field of its carbohydrate kokhmponent or a proteinaceous part (see. Hemorrhagic diathesis, tab.). A wedge, manifestations of disturbance of a blood coagulation at the same time often are absent, pathology comes to light accidentally. At nek-ry hereditary anomalies F., according to 3. S. Barkagana (1983), insignificant bleeding is observed, at others — tendency to fibrinferments (see). Structure F. in blood it can be changed as a result of activation of a fibrinolysis or formation of thrombin. The decomposition products F appearing at effect of plasmin., or fibrin-monomers, arising iod influence of thrombin, form with native F. soluble complexes (see Parakoagulyation, t. 25, additional materials). On properties F. in blood heparin exerts impact (see). At activation of anticoagulative system of blood the heparin coming to a blood stream forms with F. the complexes having high antithrombic, antinolimerazny and non-enzymatic fibrinolitic activity. Increase in contents F. in blood it is noted at various diseases: inflammatory processes, diseases of kidneys, liver, coronary heart disease, myocardial infarction, etc. Change of contents F. in a blood plasma has often differential and diagnostic and predictive value. According to Peele-gerema (L. Lake of Piigeram, 1968), speed of exchange F. at patients with coronary heart disease increases up to 0,446 mg/ml a day, in comparison with 0,387 mg/ml at healthy faces of the same age.

There are more than 100 methods of definition of concentration F. in blood, including gravimetric, volume, a nave of lometricheskiya, chemical, electrophoretic, chronometric, immunochemical and trom-boelastog r afiches a cue. The B about l yn inst in about methods includes the two-level procedure: at first carry out

department F. from other proteins by means of its transformation into fibrin, then — quantitative definition F., at the same time most often use colorimetric and nefelometrichesky methods (see Colorimetry, Nefelometriya). Results of definition F. on thrombin time (see Thrombin) normal correlate with data immunol. method. At high content in blood of cleavage products F. the sulphitic method of definition F is recommended.

Drugs F. receive from a blood plasma of donors by method of spirit fractionation according to Kohn (the I fraction). After lyophilizing F. has an appearance of porous mass of white and creamy color. Form of release: hermetically the corked glass bottles with a capacity of 250 ml and 500 ml containing

respectively 1 g and 2 g of koaguliruyemy protein (fibrinogen). Storage at a temperature from 2 to 10 °.

T. apply as a hemostatic at giio-and afibrinogenemiya, bleedings in traumatologic, surgical, oncological practice, at massive bleedings in obstetric practice. Use F. contraindicated at fibrinferments of various etiology, the increased coagulability of blood, a myocardial infarction, disorders of microcirculation in bodies at an acute renal failure, gepatorenalnokhm a syndrome, etc. Drugs F., marked 1251, use for diagnosis of thromboses as it selectively joins in blood clots. Intravenously entered F., marked 1251, quickly is removed. The changed protein is absorbed by phagocytes (see System of mononuclear phagocytes) and is exposed to zymolysis by lysosomic hydrolases (see). Bibliography: Andreenko G. V. Dysfibrinogenemias, Laborat. business, No. 8, page 451, 1974; it e, Fibrinolysis.

(Biochemistry, physiology, pathology), page 95, M., 1979; Andreenko G. V. and On -

dorolsky L. V. A sulphitic method of definition of concentration of fibrinogen in blood, Laborat. business, No. 3, page 169, 1979; B and r to and and N 3. C. Hematogenous thrombophilias, Rubbed. arkh., t. 55, No. 8, page 88, 1983; B e l and c of e r V. A. Domains — large, functionally important blocks of molecules of fibrinogen and fibrin, in book: Biochemistry of animals and the person, under the editorship of M. D. Kursky, century 6, page 38, Kiev, 1982; Tooth and D. M. Biokhimiya's ditch of a blood coagulation, page 7, M., 1978; Kudryashov B. A. Biological problems of regulation of liquid state of blood and its coagulation, M., 1975; Mashkov -

with to and y M. D. Pharmaceuticals, p. 2, page 82, M., 1984. G. V. Andreenko.

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