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Biomedical subjects

V A Belitser

Publications and source records attributed to V A Belitser.

At least 19 recordsLinked to original sources
PubMed1987

[The role of complementary E2 and D2 centers in the reaction between fibrin and fibrinogen].

The effect of fibrinogen on the two steps of polymerization of two fibrin forms differing in the set of polymerization sites (fibrin-desAA and fibrin-desAABB) was studied. It was shown that fibrinogen inhibited the protofibril growth and fibril formation at the stage of lateral aggregation more effectively with fibrin-desAABB than with fibrin desAA. When the fibrinogen D2-site was blocked by tetrapeptide Gly-His-Arg-Pro, the key structure of the E2-site, the inhibitory activity of fibrinogen diminished. A conclusion is drawn that the high susceptibility of fibrin-desAABB to fibrinogen is due to the interaction of the E2-active site with the D2-site of the fibrinogen molecule. The concentration dependence of the tetrapeptide Gly-His-Arg-Pro-induced inactivation of fibrinogen and the effects of temperature and Ca2+ on the tetrapeptide interaction with fibrinogen were investigated.

Fibrin↗
PubMed1985

The role of fibrinogen alpha C-domains in the fibrin assembly process.

Turbidity development registration and electron microscopic observation of the assembly process of the fibrin monomer and its derivative lacking in intact alpha C-domains (monomeric X1 fragment) have shown that these domains participate in fibrin polymerization, not as structural components, but as a factor promoting the ordered process of fibrin assembly.

Animals↗
PubMed1985

[Interaction of fibrinogen with two forms of fibrin differing in the degree of activation by thrombin].

The inhibitory effect of fibrinogen in the clotting of two fibrin monomer species--f-desAA and f-desAABB--was studied. The concentration dependence of this effect for two fibrin forms was found to be of the same character. This fact indicates that the modifying influence of fibrinogen proposed earlier in relation to f-desAABB also takes place in the case of f-desAA. However, an equal inhibitory effect is achieved for f-desAA at much higher fibrinogen concentrations than that for f-desAABB. The inhibitory effect of fibrinogen is greater at higher ionic strengths for both fibrin forms, but in the case of f-desAA this effect is more pronounced. The role of fibrin polymerization sites formed after fibrinopeptides B removal in initial fibrin polymerization and in F-f-desAABB interaction is discussed.

Animals↗
PubMed1983

[Mechanism of the formation of complexes between monomer fibrin and the inhibitor of its polymerization - fragment D].

It was found that fragment D derived from fibrinogen may be coupled with the fibrin monomer to produce complexes of unstable and stable types. The native fibrin monomer forms unstable complexes; the stable ones arise when the labile peripheral domains of the fibrin molecules are reversibly modified and their specific intermolecular affinity for the thrombin-activated central domains is lowered or eliminated. Fragment D, the free peripheral domain possessing polymerization centers, is strongly bound to the modified monomer occupying the polymerization sites of its central domain. The modification was induced by using acid pH (around 3.7) or by urea or NaBr taken at concentrations which caused no denaturation. In neutral media the acid-modified monomer passes to its normal state which is accompanied by simultaneous decrease of fragment D binding and restoration of codgulability. Fragment D presumably competes with the peripheral domain for the central one. Peripheral domains of the intact monomer are predominant competitors; fragment D only reduces the rate of polymerization due to temporary complex formation. However, modification results in a formation of stable complexes and thus decreases the accumulation of polymeric fibrin.

Animals↗
PubMed1983

[Differences between the complexes formed by monomeric fibrin with fragment D and dimer D].

The paper is concerned with studies in formation of monomeric fibrin (fm) complexes with fragment D (D) of fibrinogen and dimer D (DD) of stabilized fibrin. The complexes are shown to be essentially different. The fm-D complexes are unstable, their composition is a function of D concentration in the mixture, the ultimate molar D/fm ratio is equal to 3. The fm-DD complexes are quite stable, their composition is constant: the molar DD/fm ratio is equal to 1. In mixtures containing fm, DD and different amounts of D complexes of different composition are formed but the total number of D-units in them approaches 3. A model is suggested showing interaction of fm molecules in protofibril formation with allowance for the retention of binding centres which provide the lateral link between protofibrils.

Animals↗
PubMed1982

Quantitation of the inhibitory effect of fibrinogen and its degradation products on fibrin polymerization.

Anticlotting activities of fibrinogen and its plasmin degradation products--fragments X,Y and D--have been measured. On the molar basis fragments Y and D are found equally active whereas fragment X acts about 2 times stronger. We suggest that the inhibitory effect depends on a set of specific binding sites characteristic of domain D. As fragment X possesses two such sets its activity is twice as high as that of the single-set fragments Y and D. In spite of its two domains D fibrinogen inhibits clotting much weaker than fragment X. This is probably due to the presence in fibrinogen of large COOH-terminal sections of the two A infinity-chains interfering with the inhibitory effect. The possible role of these A infinity-chain sections in fibrinogen-fibrin system is discussed.

Animals↗
PubMed1980

[Mechanism of inhibition of fibrin polymerization by fibrinogen and its active fragments].

The specific inhibition of fibrin monomer polymerization by fibrinogen and some of its degradation products shows an unusual concentration dependence. Namely, in a certain region of the inhibitor concentration scale the slope of the activity curve increases considerably with an increase in concentration to reach a high constant steepness. This peculiar relationship indicates that the mechanism of inhibition is rather complicated. It has been assumed that this mechanism includes two steps: the first, preliminary step can presumably consist in an inhibitor induced transformation of fibrin (monomer or rather intermediate polymers), while the second one--a competitively inhibiting complex formation. At low inhibitor concentrations the rate of fibrin transformation is slow and limits the delay in clotting. At higher concentrations the modification is progressively accelerated and its rate gradually ceases, influencing the extent of the inhibition. The second stage, with its linear concentration dependence, becomes therefore exclusively rate-limiting. A kinetic analysis revealed that three molecules of the inhibitor are involved in the fibrin modification act. The theoretical curve obtained on the basis of the two-step model was found to be in good agreement with the experimental data.

Fibrin↗
PubMed1980

[Inhibition of fibrin assembly by fragment D and its dimer derived from fibrinogen and stabilized fibrin. Evidence for the two-step type of inhibition].

The influence of purified fragments D and DD on fibrin monomer polymerization has been studied. When applied separately, DD is less strong an inhibitor than D. An addition of small amounts of DD to the reaction mixtures containing D does not change the inhibitory effect, when the concentration of the latter fragment is low. At high concentrations of D the contribution of DD becomes more pronounced. Small amounts of D added to DD-containing systems strongly enhances the inhibition. These properties of the D--DD mixtures are unpredictable and puzzling; they contradict the generally accepted view that the specific inhibitors of fibrin polymerization, to which D and DD belong, act in a simple competitive way. The whole incomprehensible situation may be clarified in terms of a hypothesis on a two-step mechanism of inhibition. It is assumed that at the first (preliminary) step of the inhibitor effect DD is less competent than D, whereas at the second step DD possessing a high affinity for the fibrin monomer, functions as the most effective competitive inhibitor.

Animals↗
PubMed1978

[Properties of 2 fibrin monomer species which differ in the degree of thrombin activation. Characteristics of successively appearing active sites].

Some properties of intermediate and final products of fibrinogen activation by thrombin have been studied. The intermediate (fB) lacks peptide A, the final fibrin (fo)--A and B peptides. Peculiar pH-dependent differences have been observed when examining the effect of ionic strength on polymerization rate of fo and fB. Intermolecular links present in fo polymer are found to be stronger than those of fB polymer. Curves of clot turbidity vs pH for fo and Fb do not coincide. Considering these results together with the literature data on the fibrin-polymer H-bond system one may assume that there are much more H-bonds in fo polymer than in its fB variant. Polymerization of fB has been found to be practically unaffected by higher NaCl concentrations which activate fo polymerization. Our and literature evidence lead to the conclusion that the active site (contact region), generated by the release of the peptide A, effects polymerization through electrostatic and H-bonding, whereas on the removal of the peptide B another active site arises of which a system of H-bonds and hydrophobic interactions are characteristic.

Animals↗
PubMed1978

[Properties of 2 fibrin monomer forms which differ in the degree of thrombin activation. Relation of these 2 forms to specific polymerization inhibitors].

The inhibitory effect of fibrinogen and its fragment D on the clotting of two fibrin monomer species has been studied. One of them (f0) lacks peptides A and B, the other (fB) preserves peptides B. The inhibitors retard the clotting of f0 but fail to influence fB polymerization. This means that the peptide B removal and appearance of the active site B in the central (E) domain of the fibrin molecule is a prerequisite for the inhibitory effect of fibrinogen or fragment D. The specificity of this effect suggests that fragment D and the periferal D-domains of fibrinogen possess a special site (B') which reacts selectively with the fibrin active site B to block polymerization. The present investigation has demonstrated the importance of the H-bond system formation for B-B' sites interaction.

Binding Sites↗