Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factor XII was purified approximately 14 000-fold from bovine plasma by ammonium sulfate fractionation followed by heparin-agarose, DEAE-Sephadex, CM-cellulose, arginine-agarose, and benzamidine-agarose column chromatography. By this method, about 15 mg of protein was purified from 15 L of plasma with an overall yield of 18%. The purified protein was homogeneous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino-terminal analysis. Bovine factor XII is a glycoprotein with a mol wt of 74 000 as determined by sedimentation equilibrium centrifugation. It contains 13.5% carbohydrate including 3.4% hexose, 4.7% N-acetylhexosamine, and 5.4% N-acetylneuraminic acid. Factor XII is a single polypeptide chain with an NH2-terminal sequence of Thr-Pro-Pro-Trp-Lys-Gly-Pro-?-Lys-His. This sequence is homologous to the reactive-site regions of a number of protease inhibitors. The amino acid sequence of a carboxyl-terminal fragments prepared by cyanogen bromide digestion was found to be Leu-Cys-Ala-Gly-Phe-Leu-Glu-Gly-Gly-Thr-Asp-Ala-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro-Leu-Val-Cys-Glu-Asp-Glu. This sequence is homologous with the active site of a number of plasma serine proteases including thrombin, factor IXa, factor Xa, and plasmin. These data indicate that bovine factor XII is a precursor to a serine enzyme with an inhibitor sequence and a catalytic site located in the same single polypeptide chain.
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PMID:Isolation and characterization of bovine factor XII (Hageman factor). 86 Dec 10

The contact phase of intrinsic clotting involves Factor XI, Factor XII, Fletcher factor, and a fourth activity that we call contact activation cofactor (CAC). All four of these activities are reduced or absent in Dicalite-adsorbed plasma. A modified activated partial thromboplastin time assay for CAC has been defined by using a substrate of Dicalite-adsorbed plasma combined with partially purified sources of Factors XI and XII, and Fletcher factor. The following properties of CAC in plasma have been determined by using the assay: it is stable up to 60 min at 56 degrees C; gradually loses activity at 80 degrees C; is stable between pH 6 and 9; is precipitated by ammonium sulfate between 40% and 50% saturation; is slightly adsorbed by A1(OH)3; and is eluted from DEAE-cellulose after the major protein peaks. A purification procedure has been devised that separates CAC from other known clotting factors. Isolated CAC was less stable than CAC in plasma, but in the presence of dilute human serum albumin it retained full activity for 80 min at 56 degrees C. On gel filtration CAC had an apparent mol wt of 220,000 daltons. These properties are consistent with those described for Fitzgerald factor, which further supports the conclusion that CAC and Fitzgerald factor represent the same activity. Isolated CAC promoted the generation of activated Factor XI (XIa) in a mixture containing purified Factor XI, Factor XII, and kaolin. The amount of Factor XIa generated was proportional to the amount of added CAC. No time-consuming reaction between Factor XI or Factor XII and CAC could be demonstrated.
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PMID:Partial purification and characterization of contact activation cofactor. 118 36

Blood coagulation may be activated by the extrinsic or intrinsic pathways. The extrinsic clotting system is put into action by tissue thromboplastin, originating from injured tissue cells, but also from damaged leukocytes and erythrocytes. Tissue thromboplastin is a phospholipoprotein with an enzymatic component, capable of converting the clotting factor VII to its activated form, factor VIIa, which in turn activates factor X. The factor Xa-complex (containing also factor Va, phospholipid, and calcium) is the prothrombinconverting principle. The intrinsic clotting system is based on factors which are contained in the circulating blood. Its activation requires the availability of phospholipid and of activated factor XII (factor XIIa), or factor XIa. Factor XII is activated by collagen, i.e., whenever the vascular endothelium is injured, and to a lesser extent also by "activated" blood platelets. Platelets in turn are activated primarily by thrombin, collagen, and, in a self-perpetuating process, since all these materials are released from activated platelets, also by adenosine-5-diphosphate, adrenaline, and serotonin. The activation of platelets leads to a variety of morphological and biochemical alterations, culminating in their aggregation and in the selective release from storage organelles of different substances, among them those mentioned above. Of particular importance is the fact that in the course of platelet alterations, procoagulant phospholipid also becomes available on the platelet surface. The significance of the activation of the intrinsic system is seen in the possibility of the initiation of a self-sustained process which, after a primary event, e.g. vascular or cellular injury, will continue to convert prothrombin into thrombin. The effects of endotoxin on the blood clotting system show striking species differences. In the rabbit, endotoxin, with the involvement of factors of the complement system, will directly act upon blood platelets and thus initiate intravascular, intrinsic coagulation. In man, endotoxin remains without a direct effect on platelets and alternative possibilities of initiating thrombin formation must be considered. One possibility is extrinsic activation via tissue thromboplastin from injured leukocytes. Another pathway, which is supported by several experimental findings, starts out with endotoxin-mediated endothelial damage. Endothelial cells are in fact severely affected by endotoxin and may even be removed from the vascular wall, thus making accessible the subendothelial activator of factor XII. Thrombin in turn affects the vascular endothelium: therefore, one initiated, the process of intravascular activation of coagulation will perpetuate, this the more as platelets in turn will be stimulated into activity. The possible intervention of other vasoactive factors must also be considered...
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PMID:[Activation of the blood coagulation system during gram-negative infections and endotoxemias]. 122 91

A blood coagulation factor, Factor XIII, was highly purified from bovine fresh plasma by a method similar to those used for human plasma Factor XIII. The isolated Factor XIII consisted of two subunit polypeptides, a and b chains, with molecular weights of 79,000 +/- 2,000 and 75,000 +/- 2,000, respectively. In the conversion of Factor XIII to the active enzyme, Factor XIIIa, by bovine thrombin [EC 3.4.21.5], a peptide was liberated. This peptide, designated tentatively as "activation peptide," was isolated by gel-filtration on a Sephadex G-75 column. It contained a total of 37 amino acid residues with a masked N-terminal residue and C-terminal arginine. The whole amino acid sequence of "Activation peptide" was established by the dansyl-Edman method and standard enzymatic techniques, and the masked N-terminal residue was identified as N-acetylserine by using a rat liver acylamino acid-releasing enzyme. This enzyme specifically cleaved the N-acetylserylglutamyl peptide bond serine and the remaining peptide, which was now reactive to 1-dimethylamino-naphthalene-5-sulfonyl chloride. A comparison of the sequences of human and bovine "Activation peptide" revealed five amino acids replacements, Ser-3 to Thr; Gly-5 to Arg; Ile-14 to Val; Thr-18 to Asn, and Pro-26 to Leu. Another difference was the deletion of Leu-34 in the human peptide. Adsorption chromatography on a hydroxylapatite column in the presence of 0.1% sodium dodecyl sulfate was developed as a preparative procedure for the resolution of the two subunit polypeptides, a or a' chain and b chain, constituting the protein molecule of Factor XIII or Factor XIIIa. End group analyses on the isolated pure chains revealed that the structural change of Factor XIII during activation with thrombin occurs only in the N-terminal portion of the a chain, not in the N-terminal end of the b chain or in the C-terminal ends of the a and b chains. From these results, it was concluded that the activation of bovine plasma Factor XIII by thrombin must be accompanied by a limited proteolysis of the arginyl-glycyl bond located in the N-terminal region of the a chain, liberating the "Activation peptide." The possibility of activating Factor XII with other porteinases was examined using Factor Xa [EC 3.4.21.6], Factor XIIa, kallikreins [EC 3.4.21.8], urokinase [EC 3.4.99.26], trypsin [EC 3.4.21.4], ficin [EC 3.4.22.3], papain [EC 3.4.22.2], and bromelain [EC 3.4.22.4]. Among these enzymes, only bromelain and trypsin showed clear activating effects.
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PMID:On the activation of bovine plasma factor XIII. Amino acid sequence of the peptide released by thrombin and the terminal residues of the subunit polypeptides. 122 22

Researchers from Gainesville, Florida compared data on 20 women who were randomly assigned the triphasic oral contraceptive (OC) Triphasil (ethinyl estradiol and levonorgestrel) with data on 24 women who were randomly assigned the triphasic OC Ortho-Novum (ethinyl estradiol and norethindrone) and data on 8 women who were controls to evaluate these 2 triphasic OCs' effects on coagulation and anticoagulation factors. They measured these factors at baseline and 6 and 12 months after beginning OC use. Both OCs significantly reduced prothrombin time (Triphasil at 6 and 12 months, p.001; Ortho-Novum at 6 months, p01, and at 12 months, p.001). They also decreased partial thromboplastin time (Triphasil at 6 months, p.01), and at 12 months, p.001; Ortho-Novum at 6 months, p.01). Both OCs significantly increased Factor XII after 6 and 12 months (Triphasil p.001 and p.01 for controls and p.05 from baseline, respectively; Ortho Novum p.01). Ortho-Novum considerably increased fibrinogen antigen at 6 and 12 months (p.05 and p.001 from baseline and p.05 for controls, respectively) while Triphasil increased it only at 12 months (p.05). Platelet counts remained the same. Ortho-Novum markedly increased antithrombin III activity after 6 months (p.05). Even though neither OC changed antithrombin III antigen, they did significantly increase alpha-1-antitrypsin antigen and plasminogen antigen and activity at 6 and 12 months as well as alpha-2-antiplasmin antigen at 12 months. Ortho-Novum increased alpha-s-antiplasmin antigen at 12 months. No great differences in coagulation or anticoagulation factors existed between the OCs. The mean values were within reference ranges. These results showed that the OCs had the same, limited effects on hemostasis and changes in coagulation factors offset changes in anticoagulation factors.
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PMID:Changes in coagulation and anticoagulation in women taking low-dose triphasic oral contraceptives: a controlled comparative 12-month clinical trial. 144 74

Anticoagulant effects of the three LMW heparins (LMWHs) Enoxaparine, Fragmin, Logiparin and of unfractionated heparin (UFH) were compared. The heparins were added to plasma to nominal concentration of 0.2 and 0.5 anti XaU/ml plasma. Dilute tissue thromboplastin (TTP) and CaCl2 were added to platelet poor plasma (PPP), platelet rich plasma (PRP) and citrated blood. Thrombin activity was recorded with chromogenic substrate. In PPP, UFH was definitely more inhibitory than LMWH. In PRP, 0.2 U/ml of LMWHs were about as effective as UFH. At 0.5 U/ml PRP, UFH and Logiparin were more effective than Enoxaparine and Fragmin. Factor XII deficient plasma was very sensitive to heparin, and UFH and Logiparin were again more inhibitory. In whole blood, fibrinopeptide A determinations showed that UFH was more inhibitory than LMWH. We conclude that the net anticoagulant effects of these heparins result from interactions with platelets in addition to accelerated inactivation of clotting factors. The in vivo anticoagulant effect of these drugs can therefore not be predicted from their nominal anti Xa and anti IIa effects alone.
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PMID:Involvement of the extrinsic pathway in the activities of low molecular weight heparins. 165 67

A patient with known factor XII deficiency underwent extraction of four impacted third molars. Significant preoperative laboratory values included a partial thromboplastin time (PTT) of greater than 100 seconds and a factor XII level of less than 1%. The third molars were removed without any significant intraoperative or postoperative bleeding. Factor XII not only has an important function in the initiation of the intrinsic pathway of the coagulation cascade, but it also plays a significant role in complement activation, kinin generation, and fibrinolysis. It would seem that a deficiency in this factor would have widespread clinical implications. In fact, the only clinical significance seems to be a predisposition to thromboembolism in factor XII deficient patients.
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PMID:Clinical implications of factor XII deficiency. 277 71

In a clinical, between-patient study we investigated the effects of a VLMW Heparin fragment (CY 222) versus standard heparin (SH) in plasma exchanges (n = 10) on coagulation factors (CF). Fibrinogen (FGN), II, V, VIIF + X, IX, XI, XII, VIIIc, VIIIRag, VIIIvwf and ATIII, ProtC, ProtS, Plasminogen (PGN), Activated Thromboplastin time (APTT), Prothrombin time (PT), Thrombin time (TT), anti factor Xa (Axa), DDimer, Platelet count. Heparin was administered as a bolus and by infusion during the session, CY 222 as a bolus dose only; 1 to 1.5 plasma volume was exchanged with substitution by 5% albumin. Results (mean, s.d.) at the end of the session (End) and 4 hours later (T4) were analyzed and showed no differences between groups (with CY 222 and with SH) for technical and clinical findings. Biologically, CF were similar in both groups except for Factor XII levels at the end of the session, and Factors II, V, XII at T4. Prolonged APTT in all samples appear related to low FGN. Significant differences in Axa activities were found for each treatment when compared with its own standard, suggesting different ranges of activities of both drugs. Changes in D-dimer levels differed during the session and four hours after the session with the drug tested, and could be related to their mode of administration. Clinical efficiency and tolerance were excellent both with CY 222 and SH.
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PMID:[Plasma exchange with very low molecular weight heparin CY 222. Biological profile and therapeutic value]. 285 13

Hageman factor (HF, Factor XII) is activated by glass, collagen, and ellagic acid, and initiates blood coagulation via the intrinsic pathway. C1q inhibits collagen-induced platelet aggregation and adherence of platelets to glass, effects attributable to the collagen-like region of C1q. We examined the actions of C1q on HF activation. Incubation of C1q with HF before addition of HF-deficient plasma extended the activated partial thromboplastin time. Similarly, when glass tubes were coated with C1q before testing, the partial thromboplastin time of normal plasma was increased. C1q reduced the activation of HF by ellagic acid, as measured by the release of p-nitroaniline from the synthetic substrate H-D-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide dihydrochloride, an effect inhibited by monoclonal anti-human C1q murine IgG and by digestion of C1q by collagenase. Thus, C1q inhibits activation of HF in vitro in clot-promoting and amidolytic assays and suggests a regulatory mechanism for the inhibition of coagulation.
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PMID:Inhibition of the activation of Hageman factor (factor XII) by complement subcomponent C1q. 303 61

Suspensions of peripheral blood mononuclear cells (PBMC), monocytes, T or B lymphocytes, platelets or granulocytes, and cell-depleted supernatant fluids of these suspensions inhibited activation of Hageman factor (HF, Factor XII) by ellagic acid, a property not shared by erythrocytes. PBMC also inhibited HF activation by glass or sulfatides. Contaminating platelets may have contributed to inhibition by PBMC. Elaboration of agents inhibiting HF activation required metabolically active cells. The inhibitor(s) in PBMC supernates were not identified with known agents, but had properties of a nonenzymatic protein. PBMC supernates did not contain fibrinogen, nor alter the thrombin, prothrombin, or partial thromboplastin times of normal plasma, amidolysis by activated plasma thromboplastin antecedent (Factor XIa) or activated Stuart factor (Factor Xa) or esterolysis by C1 (C1 esterase); they inhibited plasmin minimally. These experiments suggest that peripheral blood cells may impede intravascular coagulation. Whether this property helps maintain the fluidity of blood is unclear.
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PMID:Inhibition of the activation of Hageman factor (factor XII) by peripheral blood cells. 349 41


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