Cross-linking of fibrinogen and fibrin by fibrin-stablizing factor (factor XIIIa).
Factor XIIIa catalyzed intermolecular cross-linking of fibrinogen at initial rates that varied in direct (first order) proportion to the fibrinogen concentration, which differed from the well known zero order relationship in fibrin cross-linking. Preferential cross-linking of gamma-chains occurred with both substrates. The differences in rates and order of reaction were attributed mainly to effect of self-alignment of the gamma-chains in fibrin which enabled the cross-linking enzyme to interact with paired chains as a single rather than two independent entities. Studies on mixtures of fibrinogen and fibrin indicated factor XIIIa had near equal affinities for the two substrates. At low concentrations with which cross-linking of fibrinogen proceeded sluggishly compared to fibrin, fibrinogen inhibited stabilization of fibrin clots by competitively partitioning factor XIIIa away from the fribin. Additional inhibition arose from cross-linking of fibrin in soluble combination with fibrinogen in mixtures containing fibrinogen in large excess over fibrin. The observations demonstrate ways in which fibrinogen normally helps to suppress both polymerization and cross-linking of small amounts of fibrin produced within the circulation. At very high concentrations above 30 mg. per milliliter, fibrinogen underwent cross-linking at faster initial rates than the cross-linking of fibrin. Rapid cross-linking of concentrated fibrogen raises the possibility that filtration enrichment may be a factor contributing to abnormal formation of the highly insoluble fibrinogen deposits occurring in atheromatous tissue.
D000818:Animals; D001777:Blood Coagulation; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002850:Chromatography, Gel; D003720:Densitometry; D003864:Depression, Chemical; D004591:Electrophoresis, Polyacrylamide Gel; D004952:Esters; D005176:Factor XIII / Q000494:pharmacology; D005337:Fibrin; D005340:Fibrinogen; D005782:Gels; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides; D011108:Polymers; D013057:Spectrum Analysis; D014461:Ultracentrifugation
D004952:Esters; D005782:Gels; D009842:Oligopeptides; D011108:Polymers; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D005998:Glycine