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At least 19 recordsLinked to original sources
PubMed1976

Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma.

Prekallikrein and high-molecular-weight kininogen were found associated in normal human plasma at a molecular weight of 285,000 as assessed by gel filtration on Sephadex G-200. The molecular weight of prekallikrein in plasma that is deficient in high-molecular-weight kininogen was 115,000. This prekallikrein could be isolated at a molecular weight of 285,000 after plasma deficient in high-molecular-weight kininogen was combined with plasma that is congenitally deficient in prekallikrein. Addition of purified 125I-labeled prekallikrein and high-molecular-weight kininogen to the respective deficient plasma yielded a shift in the molecular weight of prekallikrein, and complex formation could be demonstrated by incubating prekallikrein with high-molecular weight kininogen. This study demonstrates that prekallikrein and high-molecular-weight kininogen are physically associated in plasma as a noncovalently linked complex and may therefore be adsorbed together during surface activation of Hageman factor. The complex is disrupted when these proteins are isolated by ion exchange chromatography.

Factor XII↗
PubMed1979

Occurrence of Leu-Lys-bradykinin and histidine-rich peptide in high-molecular-weight kininogen isolated from horse plasma.

On incubation of purified horse plasma high-molecular-weight kininogen with purified plasma kallikrein, three new peptides, named fragment 1.2, fragment 1 and fragment 2, were released, in addition to the vasopeptide, bradykinin. Fragment 2 contained an extremely high level of histidine, in which eleven residues out of the total 48 residues were characterized. Thus the result proves the existence of the histidine-rich region in horse high-molecular-weight kininogen, which is similar to the region previously identified in bovine high-molecular-weight kininogen. Moreover, we have identified a new kinin derivative, Leu-Lys-bradykinin, in horse high-molecular-weight kininogen.

Amino Acid Sequence↗
PubMed1977

Role of high-molecular-weight kininogen in surface-binding and activation of coagulation Factor XI and prekallikrein.

In the contact phase of activation of the kinin-forming, intrinsic clotting, and fibrinolytic systems, high-molecular-weight kininogen acts as a cofactor for the activation of Factor XI, prekallikrein, and Hageman factor. One mechanism by which high-molecular-weight kininogen acts as a cofactor has been studied by using 125I-labeled Factor XI and prekallikrein in kaolin-activated normal human plasma and plasmas deficient in high-molecular-weight kininogen and Hageman factor. High-molecular-weight kininogen was found to be essential for normal binding and cleavage of both Factor XI and prekallikrein on the kaolin surface. Hageman factor was essential for cleavage but not for binding of Factor XI and prekallikrein to kaolin. In normal plasma 80% of the activated Factor XI remained surface-bound, whereas 80% of the kallikrein was not surface-bound. These findings are consistent with the hypothesis that, in the initial phase of contact activation, high-molecular-weight kininogen links both Factor XI and prekallikrein to the exposed surface where they are activated by surface-bound activated Hageman factor. Once activated, the Factor XI molecules remain localized at the site of activation, in contrast to the kallikrein molecules which are found largely in the surrounding plasma.

Adult↗
PubMed1977

The carbohydrate structure of a glycopeptide released by the action of plasma kallikrein on bovine plasma high-molecular-weight kininogen.

Fragment 1, released from bovine plasma high-molecular-weight kininogen by the action of plasma kallikrein, is a glycopeptide with approximately 3 mol of each of N-acetylgalactosamine, galactose and sialic acid in one molecule. All these sugars were in the T-1 fragment obtained by tryptic digestion of fragment 1. Sialic acid can be completely released from the T-1 fragment by sialidase digestion. When this sialic acid-free T-1 fragment was incubated with purified diplococcal endo-alpha-N-acetylgalactosaminidase, all remaining sugars were released as a disaccharide. By Smith degradation and beta-galactosidase digestion, the structure of this disaccharide was found to be Gal beta 1 leads to 3GalNAc. Methylation analysis of the trisaccharide released from fragment T-1 by alkaline borohydride treatment indicated that all the galactose was obtained as the 2,4,6-tri-O-methyl derivative. Based on this evidence, the complete structure of the carbohydrate moieties of fragment 1 was proposed as Sialyl alpha 2 leads to 3Gal beta 1 leads to 3GalNAc. In addition, small amounts of a tetrasaccharide, Sialyl alpha 2 leads to 3Gal beta 1 leads to 3(Sialyl alpha 2 leads to 6)GalNAc also occurred as a carbohydrate chain of fragment 1.

Animals↗
PubMed1975

Studies on the primary structure of bovine high-molecular-weight kininogen. Amino acid sequence of a fragment ("histidine-rich peptide") released by plasma kallikrein.

An unknown peptide fragment, which was released from bovine high-molecular-weight kininogen by bovine plasma kallikrein [EC 3.4.21.8], was isolated and its chemical structure was established. The fragment consisted of 41 amino acids with serine and arginine at the NH2- and COOH-termini, respectively. The molecular weight was calculated to be 4,584. It was very basic and contained eleven residues each of histidine and glycine and seven residues of lysine. Thus, the total number of these three amino acids accounted for about 70 percent of the total residues constituting the fragment. The amino acid sequence of the fragment, designated tentatively as "His-rich peptide," was studied by Edman degradation and standard enzymatic and chemical techniques. These data made it possible to deduce the following sequence: H-Ser-His-Gly-Leu-Gly-His-Gly-His-Gln-Lys-Gln-His-Gly-Leu-Gly-His-Gly-His-Lys-His-Gly-His-Gly-His-Gly-Lys-His-Lys-Asn-Lys-Gly-Lys-Asn-Asn-Gly-Lys-His-Tyr-Asp-Trp-Arg-OH. The fragment had an extremely interesting feature in that repeating sequences occur along the peptide chain. The repeats were of the type His-Gly-X or Gly-His-X and this sequence appeared six or seven times up to 26 residues from the N-terminal end. Moreover, three tetrapeptide sequences of Gly-His-Gly-His and two heptapeptide sequence consisting of His-Gly-Leu-Gly-His-Gly-His were found in the N-terminal portion. It should be noted that plasma kallikrein liberates such a histidine-rich peptide from the kininogen in addition to a physiologically active peptide, bradykinin. The location of the "His-rich peptide" fragment in the percursor protein is also discussed.

Amino Acid Sequence↗
PubMed1976

Primary structure of bovine plasma high-molecular-weight kininogen. The amino acid sequence of a glycopeptide portion (fragment 1) following the C-terminus ot the bradykinin moiety.

On incubation of bovine plasma high-molecular-weight (HMW) kininogen with purified plasma kallikrein [EC 3.4.21.8], a large glycopeptide fragment and the vasoactive peptide, bradykinin, were initially liberated; the former, named fragment 1-2, was subsequently cleaved into fragment 1 (glycopeptide) and the previously established fragment 2 (histidine-rich peptide). The isolated fragment 1-2 contained a total of 108 to 110 amino acid residues and carbohydrates, and the amino-terminal sequence Ser-Val-Gln was established. The other fragment, fragment 1, consisted of a total of 69 amino acid residues with serine and arginine (and lysine) at the amino and carboxyl termini, respectively. It contained eleven residues each of histidine and glycine, together with an oligosaccharide chain consisting of galactosamine, hexose and sialic acid. The complete amino acid sequence of fragment 1 was determined by Edman degradation and standard enzymatic and chemical techniques. These results established the following sequence: H-Ser-Val-Gln-Val-Met-Lys-Thr-Glu-Gly-Ser-Thr-Pro/Thr-Val-Ser(CHO)-Val/Leu-Pro-His-Ser-Ala-Met-Ser-Pro-Val-Gln-Asp-Glu-Glu-Arg-Asp-Ser-Gly-Lys-Glu-Gln-Gly-Pro-Thr-His-Gly-His-Gly-Trp-Asp-His-Gly-Lys-Gln-Ile-Lys-Leu-His-Gly-Leu-Gly-Leu-Gly-His-Lys-His-Lys-His-Asp-Gln-Gly-His-Gly-His-His-Lys/ArgOH.

Amino Acid Sequence↗
PubMed1976

[Purification and properties of high-molecular-weight rabbit kininogen].

A preparation of high-molecular weight kininogen (HMWK) was isolated from rabbit citrate blood plasma and purified using chromatography on DEAE-Sephadex A-50 and CM-Sephadex C-50. From 1 mg HMWK, trypsin or kallikreine of human blood plasma release 10 mkg bradykinine. The HMWK preparation is homogeneous during electrophoresis in 7.5% polyacrylamide gel in tris-glycine buffer, pH 8.3; its electrophoretic mobility corresponds to that of alpha2-globulins. The molecular weight of HMWK estimated using the collumn with Sephadex G-200, is 130.000--150.000; the sedimentation constant S20w is 7.6. Rabbit HMWK is neither a dimer, nor a trimer of low molecular weight kininogen (LMWK), since it does not degrade into subunits after treatment by 2.5% solution of sodium dodecyl sulfate, containing 8 M urea. 0.05 M 2-mercaptoethanol and 8 M urea induce HMWK splitting into 2 fragments with respective molecular weights of 80.000 and 30.000, the kinine-containing group being localized in the low-molecular weight fragment. Estimation of rates of kinine formation by different kininogenasses from highly purified HMWK and LMWK preparations showed that those kininogens are functionally different substrates, since blood plasma kallikreines release kinines from HMWK at a greater rates, whereas tissue kallikreines, e. g. human saliva kallikreine release kinines from LMWK. The specificity of kallikreines as kininogenase, to trypsin, was determined. Tripsin removes bradykinine from both kininogens at the same rates, which are an order of magnitude less than those found for kallikreines.

Animals↗
PubMed1979

Specific isolation of biologically-active peptides by means of immobilized anhydrotrypsin and anhydrochymotrypsin.

Anhydrotrypsin, a derivative of bovine trypsin, immobilized on Sepharose tightly adsorbs various peptides containing L-arginine at the carboxyl termini, such as bradykinin and tuftsin. These peptides correspond to the specific products of the action of trypsin-like enzymes. Native trypsin immobilized on Sepharose does not show such strong affinity. Fragment 2, a peptide with 41 amino acid residues, which has been released together with bradykinin from bovine high-molecular-weight kininogen by the action of plasm kallikrein, is also adsorbed on the immobilized anhydrotrypsin. When only the carboxyl-terminal arginine is removed with carboxy-peptidase B, however, the peptide loses its adsorptive ability. Immobilized anhydrochymotrypsin, on the other hand, exerts specific affinity for the peptides which correspond to the products of chymotrypsin. These results suggest that the anhydro-derivatives of serine-proteseas in general may be of great use in the affinity chromatography of respective series of various naturally occurring peptides.

Amino Acid Sequence↗
PubMed1992

Prekallikrein activation in human, bovine, and rabbit plasmas: presence of an inhibitor in bovine plasma.

Contact of human plasma with a negatively charged surface such as dextran sulfate activates prekallikrein to kallikrein, which releases the vasoactive peptide bradykinin from high-molecular-weight kininogen. The dextran sulfate-induced activation of prekallikrein at 0 degree C (assayed by its amidolytic activity on the chromogenic substate S-2302) could not be observed in either bovine or rabbit plasmas when compared to human plasma. Neither bovine nor rabbit plasma inhibited the amidolytic activity of contact-activated human plasma at 0 degrees C. The activation of prekallikrein in human plasma was significantly inhibited by the addition of bovine plasma but not by rabbit plasma. Bovine plasma (0.025 units, 1 unit = 1 ml of plasma) caused 68.8% inhibition of prekallikrein activation. Eighty percent of the inhibitory property of bovine plasma was present in the greater than 30,000-molecular-weight fraction. These results indicate the presence of an inhibitor(s) of prekallikrein activation in bovine plasma.

Animals↗
PubMed1992

Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris.

BACKGROUND AND METHOD: The role of thrombus formation in the pathogenesis of acute myocardial infarction (AMI) and unstable angina pectoris has been well established. However, comprehensive and systematic studies of the blood coagulation, fibrinolytic, and inhibitory proteins are not available in patients with these conditions. Fourteen patients with AMI, 10 patients with angina pectoris, and 32 normal volunteers were studied. Plasma antigen concentrations and/or activities of high-molecular-weight kininogen (HMWK), fibrinogen, fibronectin, plasminogen, D-dimer, tissue plasminogen activator (t-PA), alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, protein C, total and free protein S, antithrombin III (AT-III), von Willebrand factor (vWF), factors (F) XII, XI, IX, VIII, VII, X, V, II, and XIII, and plasma antiplasmin activity were measured using appropriate functional or immunologic assays. RESULTS: The AMI group showed a significant reduction in F XII activity, F XII activity-to-concentration ratio, and HMWK concentration. In addition, the AMI patients exhibited a significant elevation of plasma F XI activity, F IX concentration, and F IX activity, and vWF, fibrinogen, D-dimer, and t-PA concentrations. This was associated with significant reductions in F V, F II, and AT-III activity-to-concentration ratio. Many of the changes observed in AMI patients were also present in patients with angina pectoris. Furthermore, the latter group exhibited an elevation of F VIII activity, alpha 2-macroglobulin activity, and alpha 1-antitrypsin concentration and a significant reduction of antiplasmin activity despite a normal alpha 2-antiplasmin concentration. CONCLUSIONS: The observed reduction of the plasma F XII activity-to-antigen concentration ratio combined with a reduced HMWK concentration suggests intrinsic pathway activation, while the elevation of the D-dimer concentration indicates thrombin generation and fibrin formation and degradation in the AMI group. The latter changes were also present in patients with angina pectoris. Both AMI and angina groups showed several other abnormalities of the coagulation, fibrinolytic, and inhibitory systems. The results suggest the presence of a prothrombotic state associated with the activation of coagulation and fibrinolytic systems in patients with acute myocardial ischemia or infarction.

Adult↗
PubMed1992

Activation mechanism of human Hageman factor-plasma kallikrein-kinin system by Vibrio vulnificus metalloprotease.

Vivrio vulnificus, an opportunistic human pathogen, secretes a metalloprotease (VVP). The VVP inoculated into a guinea pig is known to generate bradykinin through activation of the Hageman factor-plasma kallikrein-kinin system. VVP was shown to possess the ability to activate the human system through the same mechanism as that clarified in the guinea pig system, namely, VVP converted both human zymogens (Hageman factor and plasma prekallikrein) to active enzymes (activated Hageman factor and plasma kallikrein), and the then generated kallikrein liberated bradykinin from high-molecular-weight kininogen. However, in the presence of plasma alpha 2-macroglobulin (alpha 2M), the VVP action was drastically decreased. This finding suggests that the human system might be activated only at the interstitial-tissue space which contains negligible amounts of alpha 2M or in the bloodstream of the individuals whose plasma alpha 2M level is extremely reduced.

Bacterial Proteins↗
PubMed1992

Estrogen-associated thromboembolism.

Most of the linkage of atherosclerosis and thrombosis with estrogens is epidemiologic in origin. Although the effects of estrogens on the mechanisms of hemostasis are wide ranging, many are benign; only a few may account for thrombus formation. Platelet function tests have provided extensive but contradictory data, and interpretation is limited because it is uncertain whether a rise in one or more of these parameters is a primary or secondary effect. The most consistent effects of estrogens on coagulation proteins are elevations of fibrinogen; factors II, VII, IX, X, and XII; protein C; and plasminogen. Although these elevations have been attributed to the estrogenic component in oral contraceptives, the progestogen concentration may also influence these increases. Among other coagulation proteins studied, the following are unaffected by oral contraceptive use: factors V, VIII, and XI; prekallikrein; and high-molecular-weight kininogen. In contrast, protein S values are decreased. The plasma concentration of plasmin inhibitor is unchanged, whereas both proteinase inhibitor and macroglobulin are significantly increased by oral contraceptive use. Cl esterase inhibitor is decreased in women taking oral contraceptives and correlates with the increase in Hageman factor. Antithrombin III is one plasma inhibitor for which a decrease in quantity and activity have been associated with a thrombotic tendency in humans. Although data on estrogen-associated changes in the quantity of antithrombin III have been conflicting, the ability of plasma to inhibit factor Xa is significantly reduced in a dose-dependent manner among pre- and postmenopausal estrogen users.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

The Passovoy defect: further characterization of a hereditary hemorrhagic diathesis.

We studied a coagulation abnormality present in 12 members of five kindreds who bruised easily and bled excessively after minor trauma. Their activated partial thromboplastin times were between 32 and 39 seconds (normal, 22.8 to 28.8 seconds). Prothrombin times, thrombin times, platelet-function tests and the levels of factors XII, XI, IX, VIII, prekallikrein and high-molecular-weight kininogen were normal. Within these kindreds inheritance of prolonged partial thromboplastin times followed an autosomal and probably dominant pattern. The prolonged thromboplastin times were corrected by normal plasma and by normal plasma adsorbed with celite, but there was no mutual correction between plasmas of the patients. These subjects shared a common defect in the intrinsic pathway of coagulation that we designate by the proband's surname, Passovoy.

Adolescent↗