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S V Pizzo

Publications and source records attributed to S V Pizzo.

At least 181 records · Page 10Linked to original sources
PubMed1987

Mechanism of action of inter-alpha-trypsin inhibitor.

Inter-alpha-trypsin inhibitor (I alpha I) is a unique proteinase inhibitor that can be proteolyzed by the same enzymes that are inhibited, to generate smaller inhibitors. This study examines the reactions of I alpha I with trypsin, chymotrypsin, plasmin, and leukocyte elastase. Complexes of I alpha I and proteinase were demonstrated by gel filtration chromatography. Complete digestion of I alpha I by each proteinase was not accompanied by a comparable loss of inhibition of that enzyme or a different enzyme. Following proteolysis, inhibitory activity was identified in I alpha I fragments of molecular weight 50,000-100,000 and less than 40,000. Addition of a second proteinase inhibitor prevented proteolysis. Both I alpha I and its complex with proteinase were susceptible to degradation. Kinetic parameters for both the inhibition and proteolysis reactions of I alpha I with four proteinases were measured under physiological conditions. On the basis of these results, a model for the mechanism of action of I alpha I is proposed: Proteinase can react with either of two independent sites on I alpha I to form an inhibitory complex or a complex that leads to proteolysis. Both reactions occur simultaneously, but the inhibitory capacity of I alpha I is not significantly affected by proteolysis since the product of proteolysis is also an inhibitor. For a given proteinase, the inhibition equilibrium constant and the Michaelis constant for proteolysis describe the relative stability of the inhibition and proteolysis complexes; the second-order rate constants for inhibition and proteolysis indicate the likelihood of either reaction. The incidence of inhibition or proteolysis reactions involving I alpha I in vivo cannot be assessed without knowledge of the exact concentrations of inhibitor and proteinases; however, analysis of inhibition rate constants suggests that I alpha I might be involved in plasmin inhibition.

Alpha-Globulins↗
PubMed1987

The temperature-dependent reaction between alpha 2-macroglobulin and streptokinase-plasmin(ogen) complex.

The reactions of alpha 2-macroglobulin (alpha 2M) with plasmin or streptokinase-plasmin(ogen) (SkPl) were studied as a function of temperature. alpha 2M and plasmin reacted relatively rapidly at all temperatures. The initial rates of reaction were identical at 24 and 37 degrees C. At 4 degrees C, the initial reaction rate was somewhat slower; however, the reaction was 90% complete in 2 min. The reaction of alpha 2M with SkPl was markedly temperature-dependent. Initial rates of reaction at 0 and 24 degrees C were only 3 and 40% of the rate of 37 degrees C, respectively. When these reactions occur, only the plasmin moiety is incorporated in the alpha 2M molecule. These data explain the inconsistencies in previous reports of SkPl interactions with alpha 2M, since experiments have been performed at different temperatures in various studies. In the present work, we present a model which interprets the data in terms of a possible high-energy transition state in the alpha 2M-SkPl reaction.

Fibrinolysin↗
PubMed1987

Characterization of alpha 2-macroglobulin-plasmin complexes: complete subunit cleavage alters receptor recognition in vivo and in vitro.

When human alpha 2-macroglobulin (alpha 2M) binds proteinases, it undergoes subunit cleavage. Binding of small proteinases such as trypsin results in proteolysis of each of the four subunits of the inhibitor. By contrast, previous studies suggest that reaction of plasmin with alpha 2M results in cleavage of only two or three of the inhibitor subunits. In this paper, we demonstrate that the extent of subunit cleavage of alpha 2M is a function of plasmin concentration. When alpha 2M was incubated with a 2.5-fold excess of plasmin, half of the subunits were cleaved; however, at a 20-fold enzyme to inhibitor ratio, greater than 90% of the subunits were cleaved with no additional plasmin binding. This increased cleavage was catalyzed by free rather than bound plasmin. It is concluded that this "nonproductive" subunit cleavage is dependent upon the molar ratio of proteinase to inhibitor. The consequence of complete subunit cleavage on receptor recognition of alpha 2M-plasmin (alpha 2M-Pm) complexes was studied. Preparations of alpha 2M-Pm with only two cleaved subunits bound to the murine macrophage receptor with a Kd of 0.4 nM and 60 fmol of bound complex/mg of cell protein. When preparations of alpha 2-M-Pm with four cleaved subunits were studied, the Kd was unaltered but ligand binding increased to 140 fmol/mg of cell protein. The receptor binding behavior of the latter preparation is equivalent to that observed when alpha 2M is treated with small proteinases such as trypsin. This study suggests that receptor recognition site exposure is not complete in the alpha 2M-Pm complex with half of the subunits cleaved. Proteolytic cleavage of the remaining subunits of the inhibitor results in a further conformational change exposing the remaining receptor recognition sites.

Animals↗
PubMed1987

Defective release of tissue plasminogen activator in systemic and cutaneous vasculitis.

The fibrinolytic system in a group of 23 patients with vasculitis and 10 patients with the cutaneous vasculitis atrophie blanche were studied. These patients were found to have markedly suppressed release of vascular tissue plasminogen activator (t-PA) stores whether the disease was active or in remission. The control group had releasable t-PA levels of 0.70 +/- 0.10 IU/ml of plasma. Levels of releasable t-PA in the patient population were 0.09 +/- 0.03 IU/ml for those with active vasculitis (p less than 0.0001 compared with the control group by the Student t test), 0.23 +/- 0.12 IU/ml for those with inactive vasculitis (p less than 0.001), and 0.03 +/- 0.01 IU/ml for those with atrophie blanche (p less than 0.0001). It is concluded that there is a generalized defect in plasminogen activator in a variety of vasculitides. Such a defect may contribute to the pathogenesis of lesions as well as the thromboembolic disease that may be observed in these patients.

Adult↗
PubMed1987

Pregnancy-induced changes in the fibrinolytic balance: evidence for defective release of tissue plasminogen activator and increased levels of the fast-acting tissue plasminogen activator inhibitor.

Pregnancy is accompanied by an increased risk of thromboembolic disease. One contributing factor to such disease in the nonpregnant patient is disordered fibrinolysis. It has been suggested that defective fibrinolysis may occur in pregnancy, but this defect has been poorly characterized. In the present study of 52 women with normal pregnancies and 56 nonpregnant control women, we found a marked change in levels of releasable tissue plasminogen activator in pregnant women beginning in the first trimester. Whereas nonpregnant women demonstrated releasable levels of tissue plasminogen activator of 0.74 +/- 0.15 IU/ml of plasma, in the pregnant women the amount released was only 0.06 +/- 0.02 IU/ml of plasma (p less than 0.01). These levels were observed beginning in the first trimester. Levels of the recently described fast-acting tissue plasminogen activator inhibitor increased significantly throughout pregnancy. Values ranged from 8.40 +/- 0.27 IU/ml of plasma in the first trimester to 9.92 +/- 0.09 IU/ml of plasma in the third trimester (p less than 0.05) compared with the level of 8.46 +/- 0.19 IU/ml of plasma in nonpregnant subjects. These data suggest that alterations both in releasable tissue plasminogen activator and in the fast-acting tissue plasminogen activator inhibitor contribute to the physiologic hypercoagulable state of pregnancy.

Adult↗
PubMed1987

The role of histidyl residues in zinc-induced precipitation of alpha 2-macroglobulin-proteinase complexes.

When alpha 2-macroglobulin (alpha 2M) is reacted with proteinases including trypsin, plasmin, alpha-thrombin, or with CH3NH2, each resulting alpha 2M derivative is precipitated by Zn2+ in a similar manner. By contrast, unreacted alpha 2M is not precipitated over the same Zn2+ concentration range. Zn2+-induced precipitation of alpha 2M-CH3NH2 or alpha 2M-trypsin is prevented by acylation of the protein employing the histidine-specific reagent diethylpyrocarbonate (DEP). The Zn2+-induced precipitation of alpha 2M-trypsin is prevented by acylation of the preformed alpha 2M-trypsin complex or by the reaction of acylated native alpha 2M with trypsin. Acylation of alpha 2M by treatment with DEP results in the modification of 13.5 histidyl residues per subunit of either native alpha 2M or alpha 2M-CH3NH2. Subsequent treatment with hydroxylamine reverses the modification of 10.5 histidyl residues per subunit in each protein preparation. These results indicate that histidyl residues are involved in the Zn2+-induced precipitation of alpha 2M-proteinase or alpha 2M-CH3NH2 complexes, and that these residues are accessible to extensive protein-metal interactions only after alpha 2M has undergone a major conformational change. These appear to be the same histidyl residues which, upon acylation by DEP, are responsible for recognition of alpha 2M-proteinase complexes by the acyl-low-density-lipoprotein cell surface receptor (S. V. Pizzo, P. A. Roche, S. R. Feldman, and S. L. Gonias (1986) Biochem. J. 238, 217-225).

Acylation↗
PubMed1987

Carbohydrate recognition systems in amphibians: primitive alpha 2-macroglobulin receptors.

Two alpha-macroglobulins were isolated from the plasma of the frog. Murine clearance studies were performed with these proteins after they were reacted with proteinase. These studies indicated that clearance behavior was more complex than observed with avian or human homologues, since it involved not only specific receptors for the complex, but also carbohydrate recognition. Recognition of one of these macroglobulins by both the alpha-macroglobulin receptor and carbohydrate receptors required conformational change in the inhibitor. Clearance studies were then performed in frogs to probe the nature of carbohydrate receptor recognition. Model glycoproteins were employed to avoid the problem of heterogeneous carbohydrate end groups in the alpha-macroglobulins. These studies demonstrated that the N-acetylglucosamine/mannose receptor is the major carbohydrate recognition system in frogs.

Animals↗
PubMed1986

Evaluation of p-amidinophenyl esters as potential antithrombotic agents.

Three p-amidinophenyl esters have been synthesized and characterized as irreversible inhibitors of the vitamin-K dependent proteinases; factors IXa, Xa and thrombin (Turner et al. [4]).+ In the present report we describe the in vitro and in vivo effects of these agents on standard coagulation tests in vitro and in blood from animals treated with the compounds. At a concentration of 500 microM, the three esters increased the activated partial thromboplastin time (PTT) of pooled human plasma 3 to 5-fold. The prothrombin time increased 1.4 to 3.7-fold under similar conditions. The p-amidinophenyl ester of cinnamic acid (CINN) showed the most pronounced effect on both assays. This ester also is the best inhibitor of human factors IXa and Xa, while the p-amidinophenyl ester of benzoic acid (BENZ) is a slightly better alpha-thrombin inhibitor (4). The effect of these esters on the thrombin clotting time correlated with in vitro kinetic measurements of alpha-thrombin inhibition rates. Both BENZ and CINN increased the assay endpoint more than 6-fold. The three esters also were studied using mouse plasma. A comparable effect on the PTT was noted. Intravenous administration of 300 microliter of 1 mM CINN as a single bolus in mice caused a 2.3-fold increase in the PTT which remained 1.2-fold normal 2 h later. The BENZ and alpha-methyl-cinnamic acid (MECINN) esters were somewhat less effective as predicted from their in vitro effect on the PTT. This investigation and previous studies indicate that these compounds demonstrate low toxicity at therapeutic levels. It is concluded that the p-amidinophenyl esters may be useful in antithrombotic therapy.

Amidines↗
PubMed1986

p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin.

A number of inhibitors of thrombin and factor Xa have been described; however, only one inhibitor of factor IXa has been reported. This compound, dansyl-Glu-Gly-Arg chloromethyl ketone (DEGER), inhibits porcine factor IXa with a second-order rate constant of 2.2 X 10(4) M-1 min-1. We now describe the synthesis and characterization of three p-amidinophenyl esters that inhibit human factor IXa with second-order rate constants comparable to those observed with human and bovine factor Xa and alpha-thrombin. These rate constants of inhibition, moreover, are 2-30-fold greater than observed when DEGER is employed to inhibit porcine factor IXa. Additional advantages of these derivatives include their ease of synthesis and low degree of toxicity. The p-amidinophenyl ester of benzoic acid was employed to inhibit human factor IXa, and the plasma clearance of the protein was studied in mice. These experiments demonstrate for the first time that the endothelial binding previously reported with factor IXa is independent of the active site, a finding similar to the behavior observed with factor Xa and alpha-thrombin in this and previous reports.

Acylation↗
PubMed1986

Further characterization of the platinum-reactive component of the alpha 2-macroglobulin-receptor recognition site.

alpha 2-Macroglobulin (alpha 2M)-methylamine that had been allowed to react with cis-dichlorodiammineplatinum(II) (cis-DDP) bound with greatly reduced affinity to specific alpha 2M receptors, as determined by macrophage binding studies in vitro and plasma-clearance experiments in vivo. Subsequent reaction with diethyl dithiocarbamate completely restored receptor recognition function. The optimal effect was obtained when the diethyl dithiocarbamate concentration was twice the total platinum concentration. alpha 2M-methylamine that was allowed to react with H2O2 competed less effectively for specific cell-surface binding sites, as demonstrated by studies both in vivo and in vitro. The apparent dissociation constant was increased nearly 7-fold by a 15 min exposure to H2O2. alpha 2M-methylamine was affected significantly less by the H2O2 exposure after pretreatment with cis-DDP. Amino acid analysis indicated that H2O2 treatment of alpha 2M modified 19 of the 25 methionine residues per alpha 2M subunit. Pretreatment with cis-DDP protected two to four of these methionine residues. The only other residue altered by H2O2 treatment of alpha 2M was histidine. A net decrease of two histidine residues per subunit was observed, but cis-DDP pretreatment did not alter this result. In order to rule out the slight possibility that histidine modification might account for the observed H2O2-induced loss in receptor recognition, diethyl pyrocarbonate was employed as a histidine-modifying reagent. This treatment modified 53 histidine residues in both native and fast-form alpha 2M. Fast-form alpha 2M was still recognized by the alpha 2M receptor, as determined by studies both in vivo and in vitro; however, a fraction of the modified protein now cleared via the acyl-low-density-lipoprotein receptor as well. Reaction of diethyl pyrocarbonate-treated alpha 2M with hydroxylamine reversed derivatization of 43 of the 53 histidine residues. Moreover, this treatment also resulted in an alpha 2M fast-form preparation that was recognized only by the alpha 2M receptor. It is concluded that cis-DDP and H2O2 modify a critical methionine residue in the primary sequence of the alpha 2M-receptor recognition site.

Amino Acids↗
PubMed1986

In vivo metabolism of inter-alpha-trypsin inhibitor and its proteinase complexes: evidence for proteinase transfer to alpha 2-macroglobulin and alpha 1-proteinase inhibitor.

Inter-alpha-trypsin inhibitor was purified by a modification of published procedures which involved fewer steps and resulted in higher yields. The preparation was used to study the clearance of the inhibitor and its complex with trypsin from the plasma of mice and to examine degradation of the inhibitor in vivo. Unlike other plasma proteinase inhibitor-proteinase complexes, inter-alpha-trypsin inhibitor reacted with trypsin did not clear faster than the unreacted inhibitor. Studies using 125I-trypsin provided evidence for the dissociation of complexes of proteinase and inter-alpha-trypsin inhibitor in vivo, followed by rapid removal of proteinase by other plasma proteinase inhibitors, particularly alpha 2-macroglobulin and alpha 1-proteinase inhibitor. Studies in vitro also demonstrated the transfer of trypsin from inter-alpha-trypsin inhibitor to alpha 2-macroglobulin and alpha 1-proteinase inhibitor but at a much slower rate. The clearance of unreacted 125I-inter-alpha-trypsin inhibitor was characterized by a half-life ranging from 30 min to more than 1 h. Murine and human inhibitors exhibited identical behavior. Multiphasic clearance of the inhibitor was not due to degradation, aggregation, or carbohydrate heterogeneity, as shown by competition studies with asialoorosomucoid and macroalbumin, but was probably a result of extravascular distribution or endothelial binding. 125I-inter-alpha-trypsin inhibitor cleared primarily in the liver. Analysis of liver and kidney tissue by gel filtration chromatography and sodium dodecyl sulfate gel electrophoresis showed internalization and limited degradation of 125I-inter-alpha-trypsin inhibitor in these tissues. No evidence for the production of smaller proteinase inhibitors from 125I-inter-alpha-trypsin inhibitor injected intravenously or intraperitoneally was detected, even in casein-induced peritoneal inflammation. No species of molecular weight similar to that of urinary proteinase inhibitors, 19,000-70,000, appeared in plasma, liver, kidney, or urine following injection of inter-alpha-trypsin inhibitor.

Alpha-Globulins↗
PubMed1986

The binding of fucose-containing glycoproteins by hepatic lectins. Re-examination of the clearance from blood and the binding to membrane receptors and pure lectins.

The nature of the hepatic receptors that bind glycoproteins through fucose at the non-reducing termini of oligosaccharides in glycoproteins has been examined by three different approaches. First, the clearance from blood of intravenously injected glycoproteins was examined in mice with the aid of neoglycoproteins of bovine serum albumin (BSA). The clearance of fucosyl-BSA was rapid and was not strongly inhibited by glycoproteins that inhibit clearance mediated by the galactose or the mannose/N-acetylglucosamine receptors of liver. The clearance of Fuc alpha 1,3(Gal beta 1,4)GlcNAc-BSA (where Fuc is fucose) was inhibited weakly by either Fuc-BSA or Gal beta 1,4GlcNAc-BSA but strongly by a mixture of the two neoglycoproteins, suggesting that its clearance was mediated by hepatic galactose receptors as well as by a fucose-binding receptor. Second, the binding of neoglycoproteins to a membrane fraction of mouse liver was examined. Fuc-BSA binding to membranes was Ca2+ dependent but was not inhibited by glycoproteins that would inhibit the galactose or the mannose/N-acetylglucosamine receptors. In addition, the binding of Fuc-BSA and Gal beta 1,4GlcNAc-BSA differed as a function of pH, in accord with binding of Fuc-BSA through fucose-specific hepatic receptors. Finally, the binding of neoglycoproteins to the pure galactose lectin from rat liver was examined. Neither Fuc-BSA nor Fuc alpha 1,2Gal beta 1,4GlcNAc-BSA bound the galactose lectin, although Fuc alpha 1,3(Gal beta-1,4) GlcNAc-BSA bound avidly. Taken together, these studies suggest that a fucose-binding receptor that differs from the galactose and the mannose/N-acetylglucosamine receptors may exist in rat and mouse liver.

Animals↗
PubMed1986

Purification and characterization of human alpha 2-macroglobulin conformational variants by non-ideal high performance size-exclusion chromatography.

Human alpha 2-macroglobulin (alpha 2M) was eluted as a single nondispersed peak from a TSK-G4000SW size exclusion chromatography column equilibrated in 20 mM-sodium phosphate/100 mM-NaCl, pH 7.2 (PBS). The void volume and total accessible volume of the column were 6.08 ml and 14.42 ml. The elution volume (Ve) of native alpha 2M was 9.20 +/- 0.04 ml. The Ve was altered minimally by changing the ionic strength or adding ethanol to the equilibration buffer. Ternary alpha 2M-trypsin, containing 2 mol of proteinase/mol of inhibitor, and alpha 2M-methylamine failed to be eluted in well-defined peaks when the column was equilibrated in PBS. The majority of either preparation was recovered slowly at Ve values greater than 14.5 ml, reflecting significant nonideal interactions with the support structure. Addition of 10% ethanol or increased ionic strength in the equilibration buffer independently caused either form of reacted alpha 2M to be eluted in a distinct peak at decreased Ve, suggesting that the nonideal interactions included hydrophobic and electrostatic adsorption. When the equilibration buffer was 80 mM-sodium phosphate/320 mM-NaCl, pH 7.2, partial resolution of ternary alpha 2M-trypsin and alpha 2M-methylamine was obtained with a single column run. The Ve values of ternary alpha 2M-trypsin and alpha 2M-methylamine in this buffer were 13.15 +/- 0.08 ml and 11.94 +/- 0.14 ml, respectively. The Ve of native alpha 2M was 8.84 +/- 0.03 ml. The resolving capacity of TSK-G4000SW was exploited to purify native alpha 2M rapidly and efficiently from solutions that contained significant amounts of either ternary alpha 2M-trypsin or binary alpha 2M-trypsin (1 mol of proteinase/mol of inhibitor). This purification was complete within the limits of sensitivity of denaturing and nondenaturing polyacrylamide-gel electrophoresis. alpha 2M-plasmin was well resolved from native alpha 2M. The Ve of alpha 2M-plasmin was 12.88 +/- 0.32 ml in 80 mM-sodium phosphate/320 mM-NaCl, pH 7.2. A number of procedures were used to prepare solutions with up to 90% binary alpha 2M-trypsin. The Ve of binary alpha 2M-trypsin in these various solutions was intermediate between the values of native alpha 2M and ternary alpha 2M-trypsin. The conformations of binary and ternary complex, as reflected by mobility in nondenaturing electrophoresis, were identical, confirming previous results. Finally, in the binary alpha 2M-trypsin complex, the single trypsin cleaved more than two, and as many as all four alpha 2M subunits.

Chromatography, High Pressure Liquid↗
PubMed1986

The macrophage-mediated regulation of hepatocyte synthesis of antithrombin III and alpha 1-proteinase inhibitor.

Antithrombin III (ATIII) is an anticoagulant protein which binds and inactivates thrombin and other serine proteinases. Little is known about regulation of its synthesis. We confirm that ATIII is synthesized by isolated rat hepatocytes, and that its synthesis is not altered by direct feedback of its complexes with proteinases. Neither is hepatocyte synthesis of ATIII altered by supernatants from macrophages cultured in the presence of ATIII-proteinase complexes. However, culture of macrophages with fibrinogen fragment D results in production of a factor(s) in the macrophage supernatants which stimulates hepatic fibrinogen synthesis, as previously described, and also stimulates the synthesis of ATIII and alpha 1-proteinase inhibitor (alpha 1PI). Synthesis of albumin and rat alpha 2-macroglobulin (alpha 2M) is not (alpha 2M) is not altered. Culture of macrophages in the presence of bacterial endotoxin also results in release of a factor(s) into the medium which stimulates the same changes in hepatocyte protein synthesis. These results show for the first time a mechanism by which synthesis of ATIII can be regulated during coagulation and fibrinolysis.

Animals↗
PubMed1986

Purification and characterization of a "half-molecule" alpha 2-macroglobulin from the southern grass frog: absence of binding to the mammalian alpha 2-macroglobulin receptor.

An alpha-macroglobulin (alpha 2M), which is a dimer consisting of two non-disulfide-bonded subunits, was identified and purified from frog plasma by Ni2+ chelate affinity chromatography. This frog "half-molecule" alpha-macroglobulin migrated as an alpha 2-globulin in cellulose-acetate electrophoresis rather than as the previously described frog alpha 1M, which exists as a tetramer formed by the noncovalent association of disulfide-bonded pairs. A molecular weight of approximately 380 000 was obtained by gel-filtration high-pressure liquid chromatography, and in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) the protein migrated as a single band of Mr approximately 180 000 before and after reduction. No evidence was obtained for association of this protein to a higher molecular weight species. After the preparation was heated, additional bands were obtained in SDS-PAGE with Mr approximately 60 000 and 12 000. The additional bands were not obtained after heating methylamine-treated preparations. The circular dichroic spectrum of frog alpha 2M exhibits negative ellipticity over the region 205-250 nm with a minimum at 216 nm. After reaction with proteinase, a decrease in the absolute mean residue rotation was obtained. Amino acid analysis demonstrated that frog alpha 2M and alpha 1M are similar in composition to avian and mammalian alpha-macroglobulins; however, there are sufficient differences in the composition of these two amphibian alpha-macroglobulins to support the conclusion that they are distinct proteins. Frog alpha 2M bound approximately 0.5 mol of trypsin/mol of inhibitor. This binding was abolished by pretreatment with methylamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1986

Defective release of vascular plasminogen activator in patients with gynecologic malignancies.

Vascular plasminogen activator release was measured in 176 women with gynecologic malignancies and 92 normal women. Releasable plasminogen activator was considerably decreased in the patients (P less than 0.00001 by Wilcoxon's rank sum test) with 59.1% releasing less than 0.04 Committee on Thrombolytic Agents units per milliliter of plasma after a standard venous occlusion procedure. The data were also stratified by tumor location, demonstrating that this decrease in releasable vascular plasminogen activator was seen for ovarian (P = 0.0001), endometrial (P = 0.0017), and cervical (P = 0.0063) cancers. Postoperative deep vein thrombosis, with or without pulmonary emboli, occurred in 28 patients (15.9% incidence). These patients also demonstrated markedly lower levels of releasable vascular plasminogen activator compared to control subjects (P less than 0.0001). It is suggested that defective release of vascular plasminogen activator contributes to a hypercoagulable state in patients with gynecologic malignancies and predisposes to postoperative thromboembolic complications.

Colorimetry↗
PubMed1986

A three-dimensional model of a unique proteinase inhibitor: alpha 2-macroglobulin.

alpha 2-Macroglobulin inhibits many proteinases by a unique mechanism termed "trapping" depicted in Figure 3A,B. This article details a mechanism by which a large proteinase, such as plasmin, binds in a molar ratio between 1 and 2 to 1 proteinase to inhibitor. The article also discusses the placement of the bait region in relation to the thiol-esters within this model. Future investigation is required to confirm the hypothesized mechanism of plasmin binding as well as the hypothesized location of the bait region.

Binding Sites↗