Surface activation of factor XII (Hageman factor) — Critical role of high molecular weight kininogen and another potentiator

1978 ◽  
Vol 8 (1-2) ◽  
pp. 65-72 ◽  
Author(s):  
J. Y. C. Chan ◽  
C. E. Burrowes ◽  
H. Z. Movat
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Critical Role ◽  
Surface Activation ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Hageman Factor

Functional sites of bovine high molecular weight kininogen as a cofactor in kaolin-mediated activation of factor XII (Hageman factor)

Biochemistry ◽  
1980 ◽  
Vol 19 (14) ◽  
pp. 3215-3220 ◽  
Author(s):  
Teruko Sugo ◽  
Nobuhiko Ikari ◽  
Hisao Kato ◽  
Sadaaki Iwanaga ◽  
Setsuro Fujii
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Functional Sites ◽  
Hageman Factor

Interaction between factor XII (Hageman factor), high molecular weight kininogen and prekallikrein

1976 ◽  
Vol 9 (5) ◽  
pp. 423-433 ◽  
Author(s):  
John Y.C. Chan ◽  
Flavio M. Habal ◽  
Clement E. Burrowes ◽  
Henry Z. Movat
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Hageman Factor

Role of arginine residues in the coagulant activity of high molecular weight kininogen

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 805-810
Author(s):  
JJ Chang ◽  
CF Scott ◽  
RW Colman
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Critical Role ◽  
Cleavage Sites ◽  
High Molecular Weight Kininogen ◽  
Coagulant Activity ◽  
Factor Xiia ◽  
Arginine Residues ◽  
Arginine Modification

High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a procofactor that, after cleavage by kallikrein or factor XIIa, gains ability to bind to the surface. The mechanism responsible for this increased affinity for the surface is unknown. We hypothesized that modification of arginine residues may prevent cleavage of HMW kininogen, since the initial kallikrein-induced cleavage sites on the HMW kininogen molecule are at the NH2 terminal and the COOH terminal of the bradykinin-containing portion of the molecule, each of which contains arginine. We found that modification with butanedione of four arginine residues in the HMW kininogen molecule prevented bradykinin release, which results from cleavage of HMW kininogen. Furthermore, HMW kininogen coagulant activity was lost, in proportion to the degree of arginine modification, until 6.6 residues had been modified. Complex formation with prekallikrein, however, was found to be uneffected by the modification of modified HMW kininogen. To account for the loss of coagulant activity, we also examined the ability of modified HMWKa (active cofactor) to bind to an activating surface. The affinity of modified HMWKa for kaolin was tenfold less than the affinity of unmodified HMWKa. These data suggest that arginine residues play a critical role in the ability of HMW kininogen to function as an activation cofactor, both by preventing the cleavages that produce HMWKa as well as by decreasing the affinity of HMWKa for the surface.

scholarly journals Role of arginine residues in the coagulant activity of high molecular weight kininogen

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 805-810 ◽  
Author(s):  
JJ Chang ◽  
CF Scott ◽  
RW Colman
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Critical Role ◽  
Cleavage Sites ◽  
High Molecular Weight Kininogen ◽  
Coagulant Activity ◽  
Factor Xiia ◽  
Arginine Residues ◽  
Arginine Modification

Abstract High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a procofactor that, after cleavage by kallikrein or factor XIIa, gains ability to bind to the surface. The mechanism responsible for this increased affinity for the surface is unknown. We hypothesized that modification of arginine residues may prevent cleavage of HMW kininogen, since the initial kallikrein-induced cleavage sites on the HMW kininogen molecule are at the NH2 terminal and the COOH terminal of the bradykinin-containing portion of the molecule, each of which contains arginine. We found that modification with butanedione of four arginine residues in the HMW kininogen molecule prevented bradykinin release, which results from cleavage of HMW kininogen. Furthermore, HMW kininogen coagulant activity was lost, in proportion to the degree of arginine modification, until 6.6 residues had been modified. Complex formation with prekallikrein, however, was found to be uneffected by the modification of modified HMW kininogen. To account for the loss of coagulant activity, we also examined the ability of modified HMWKa (active cofactor) to bind to an activating surface. The affinity of modified HMWKa for kaolin was tenfold less than the affinity of unmodified HMWKa. These data suggest that arginine residues play a critical role in the ability of HMW kininogen to function as an activation cofactor, both by preventing the cleavages that produce HMWKa as well as by decreasing the affinity of HMWKa for the surface.

The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy

1984 ◽  
Vol 52 (03) ◽  
pp. 221-223 ◽  
Author(s):  
M Christe ◽  
P Gattlen ◽  
J Fritschi ◽  
B Lämmle ◽  
W Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Negative Correlation ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
High Molecular Weight Kininogen ◽  
Contact Phase ◽  
Α2 Macroglobulin

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

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