SampleGelInformation:

Overview:

FactorXII(XII)(HagemanFactor)isasinglechain(Mr=78,000)glycoproteinzymogenthatcirculatesinplasmaataconcentrationof40µg/ml(1-5).RecipricalactivationofXIItotheactiveserineproteasefactorXIIa(XIIa)bykallikreiniscentraltoinitiationoftheintrinsiccoagulationpathway.Surfaceboundα-XIIainturnactivatesfactorXItoXIa.Secondarycleavageofα-XIIabykallikreinyieldsβ-XIIa,whichcatalyzessolutionphaseactivationofkallikrein,factorVIIandtheclassicalcomplementcascade.

TheABIlityofavarietyofnegativelychargedsubstances,bothphysiologicalandnonphysiologicaltopromoteXIIactivationand,thus,initiationoftheintrinsicpathwayhasledtothepsuedonym"contactactivation".Bindingtoanionicsurfacesinducesaconformationalchange,makingtheXIIzymogenmoresusceptIBLetocleavagebyavarietyofproteases(6,7).ItisunlikelythatbindingtonegativelychargedsurfacesaloneissufficienttoactivateXII,sincehighlypurifiedpreparationsofXIIandplasmadeficientinprekallikreinandhighmolecularweightkininogendonotundergothis"autocatalysis"(8-11).

AsinglecleavagebykallikreinatR353-Val354ofXIIyieldsα-XIIa,a2chainprotease(Mr=80,000)heldtogetherbydisulfidebonds.TheCOOH-terminallightchain(Mr=28,000)containsthecatalytictriad(His-40,Asp-89,Ser-191),whiletheNH2-terminalheavychain(Mr=52,000)conatinstheanionicsurfacebindingportionofthemolecule.Asecondarycleavageofα-XIIabykallikreinoutsidethedisulfidebondyieldsβ-XIIa(XIIf,BHFa,HFf,hagemanfactorfragments)(Mr=28,000),whichnolongerbindsanionicsurfaces(12).β-XIIacanactivateprekallikrein,buthaslittleprocoagulantactivity(13,14).SeveralotherminorintermediateformsofXIIaareindicatedinthefigureabove.

InhibitorsofXIIaincludeC1-INH,α2-antiplasmin,α2-macroglobulinandantithrombinIII.Atphysiologicalconcentrations,therelativeeffectivenessoftheseinhibitorsis91:4.5:3:1.5,respectively(10,16-19).TheratioofC1-INHtoXIIhasbeenimplicatedinthe"coldactivation"offactorVIIandtheconversionofprorenintoreninonstorageofplasma(20,21).

HumanfactorXIIispreparedfromfreshfrozenplasmabyimmunoaffinitychromatographyandsuppliedin50%glycerolforstorageat-20oC.

Properties:

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