A peptide released from plasma fibrin stabilizing factor in the conversion to the active enzyme by thrombin

Mikuni, Yuko; Iwanaga, Sadaaki; Konishi, Kazuhiko

doi:10.1016/0006-291x(73)91141-8

Cited by 26 publications

(11 citation statements)

References 17 publications

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“…FPA levels reached a maximum of 14 mol/liter (ϳ100%) then decreased with time to a final level of 10 mol/ liter by 20 min. 2) FXIII activation associated with a primary cleavage in the A-subunit at Arg-37 releasing an NH 2 -terminal activation peptide (54), is coincident with FPA release. FPA was first detectable (ϳ9%) when fXIII was already ϳ17% in its active transglutaminase form.…”

Section: Discussionmentioning

confidence: 99%

An Integrated Study of Fibrinogen during Blood Coagulation

Brummel

Butenas

Mann

1999

Journal of Biological Chemistry

114

116

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The rate of conversion of fibrinogen (Fg) to the insoluble product fibrin (Fn) is a key factor in hemostasis. We have developed methods to quantitate fibrinopeptides (FPs) and soluble and insoluble Fg/Fn products during the tissue factor induced clotting of whole blood. Significant FPA generation (>50%) occurs prior to visible clotting (4 ؎ 0.2 min) coincident with factor XIII activation. At this time Fg is mostly in solution along with high molecular weight cross-linked products. Cross-linking of ␥-chains is virtually complete (5 min) prior to the release of FPB, a process that does not occur until after clot formation. FPB is detected still attached to the ␤-chain throughout the time course demonstrating release of only low levels of FPB from the clot. After release of FPB a carboxypeptidase-B-like enzyme removes the carboxyl-terminal arginine resulting exclusively in des-Arg FPB by the 20-min time point. This process is inhibited by ⑀-aminocaproic acid. These results demonstrate that transglutaminase and carboxypeptidase enzymes are activated simultaneously with Fn formation. The initial clot is a composite of Fn I and Fg already displaying ␥-␥ cross-linking prior to the formation of Fn II with B␤-chain remaining mostly intact followed by the selective degradation of FPB to des-Arg FPB.Blood coagulation proceeds through a cascade of protein activation's that ultimately lead to the catalytic cleavage of fibrinogen (Fg) 1 by thrombin to the product fibrin (Fn). Fn is generated from plasma Fg (M r 340,000) which is found in blood plasma at ϳ3 mg/ml and exists as a symmetrical dimer consisting of A␣, B␤, and ␥ polypeptide chains linked by noncovalent and disulfide bonds (1-4). The two carboxyl-terminal domains of the B␤ and ␥-chains of Fg are designated "D" while the central domain which contains the amino termini of all the chains is designated "E." Clot formation which has been extensively studied in anticoagulated plasma and purified Fg occurs in a series of steps (4) initiated by thrombin cleavage of the A␣ and B␤-chains of Fg. Cleavage at A␣-16 releases fibrinopeptide (FP) A to form Fn I. The release of two FPA peptides exposes a site in the E domain that aligns with a complementary site in the D domain to form overlapping fibrils (5). This is followed by cleavage at B␤-14 releasing the two FPB peptides to form Fn II. FPB release appears to allow for lateral aggregation of the protofibrils (6, 7). The degree of lateral strand association contributes to the tensile strength of the clot, but its resistance to plasmin degradation is influenced mainly by covalent crosslinking. Cross-links are formed by the action of factor XIIIa (fXIIIa), a transglutaminase enzyme whose formation from zymogen fXIII (plasma concentration 90 nmol/liter) is also catalyzed by thrombin (8, 9). FXIII consists of an A 2 B 2 tetramer where the A subunit is acted upon by thrombin releasing an NH 2 -terminal activation peptide. Covalent isopeptide crosslinks are formed between certain adjacent ␥-carboxamido and ⑀-amino groups of glutamy...

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Section: Discussionmentioning

confidence: 99%

An Integrated Study of Fibrinogen during Blood Coagulation

Brummel

Butenas

Mann

1999

Journal of Biological Chemistry

114

116

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“…Thrombin mediates cleavage of the activation peptides (AP-FXIII) of FXIII-A from the N-terminus at position 37 [26][27][28]. Thrombin mediates cleavage of the activation peptides (AP-FXIII) of FXIII-A from the N-terminus at position 37 [26][27][28].…”

Section: Diane Nugent and Loan Hsiehmentioning

confidence: 99%

Factor XIII Deficiency

and

Hsieh

2014

Textbook of Hemophilia

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“…Thus, we showed that in the last stages of blood clotting thrombin has the dual task of converting fibrinogen to fibrin and activating FXIII. Similarly to its action on fibrinogen, thrombin could be assumed to function again as a limited protease, and this has been confirmed by isolating the activation peptide released from the factor [37,38].…”

Section: Primary Amines Prevent Clot Stabilization Without Inhibitingmentioning

confidence: 99%

Factor XIII and the clotting of fibrinogen: from basic research to medicine

Lóránd

2005

Journal of Thrombosis and Haemostasis

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A peptide released from plasma fibrin stabilizing factor in the conversion to the active enzyme by thrombin

Cited by 26 publications

References 17 publications

An Integrated Study of Fibrinogen during Blood Coagulation

An Integrated Study of Fibrinogen during Blood Coagulation

Factor XIII Deficiency

Factor XIII and the clotting of fibrinogen: from basic research to medicine

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