Shared Flashcard Set

Details

Mechanism of Blood Coagulation
Huang 1/19/11 very painful lecture
53
Biochemistry
Undergraduate 4
01/24/2011

Additional Biochemistry Flashcards

 


 

Cards

Term
trauma, VII(7), TF(III)
Definition
what factors make up the extrinsic pathway?
Term
kininogen->kallikrein->XII(12)->XI (11) -> IX (9)->VIII
Definition
what factors make up the intrinsic pathway?
Term
X(10) ->V(5)-> thrombin (II)->fibrin (I) -> XIII(13)
Definition
what factors make up the common pathway?
Term
inactive enzyme precursoer (proenzyme) activation usually involves proteolytic cleavage.
Definition
what is a zymogen?
Term
stimulatory proteins, factors V and VIII (5 & 8)
Definition
most clotting factors are trypsin-like proteases, but two are not. what are they and which factors?
Term
anionic surfaces are exposed (negatively charged)
Definition
injury to the normally anticoagulant endothelial lining of blood vessels makes it procoagulent. what charge change occurs?
Term
Hageman factor, binds directly to anionic surfaces "contact activation" it is a zymogen of the intrinsic pathway. this is the "temporary activation"
Definition
factor XII, what does it do in its initial activation?
Term
contact activated factor XII activates prekalekrein. and forms HMWK complex. kallikerin then activates XII by proteolysis. they are "reciprocally autoactivated." this is the "more permanent" activation of factor XII
Definition
what is the more permanent activation of factor XII and how does it happen?
Term
prekallikrein-high molecular weight kininogen
Definition
what does the HMWK complex consist of?
Term
factor XI (11-plasmathromoplastin antecendent) via proteolysis in the XI-HMWK complex (inrinsic path)
Definition
factor XIIa activates what?
Term
(aka plasma thromboplastin antecedent)activates factor IX (Christmas factor) by proteolysis (intrinsic path)
Definition
What does factor XI do?
Term
factor IX(christmas) in presence of VIIIa(anti hemophillic factor A) by proteolysis activates factor X(stuart-prower) (intrinsic path)
Definition
what does factor IX do?
Term
it serves as a carrier for factor VIII in circulation (intrinsic)
Definition
what does von willebrand's factor (vWF) do?
Term
factor 3/thromboplastin = a membrane receptor exposed during vascular trauma/injury. (extrinsic path)
Definition
what is tissue factor(TF)
Term
aka proconvertin, binds to TF, and is activated via protein-protein interaction. further activated by factor Xa (feedback) via proteolysis forming factor VIIa. also activated by factor IIa (thrombin)
Definition
what is factor VII?
Term
1. binding to TF (thromboplastin exposed in damaged membrane) protein-protein
2. Xa proteolysis -> VIIa
3. factor IIa (thrombin)
Definition
what 3 ways is proconvertin (factor VII) activated?
Term
VIIa or VII, incomplex with TF -> proteolysis
Definition
what activates factor X in the extrinsic path?
Term
cleaving a hexapeptide (factor VIIa, VII extrinsic or IXa + VIIIa intrinsic)
Definition
how is factor X activated (both paths)
Term
stuart prower factor -> complexed with Va(accelerin) catalyzes conversion of prothrombin(II) to thrombin(IIa)
Definition
what does Xa do?
Term
thrombin(IIa) catalyzes conversion of fibrinogen (factor I) to fibrin (Ia) forming the soft clot
Definition
What does factor II do?
Term
transglutamidase/fibrin stabilizing factor catalyzes cross-linking of fibrin monomers to yield the hard clot (accompanied by clot retraction)
Definition
what does factor XIII do?
Term
prothromb. is cut between disulfide bond near gamma-carboxyglutamate, then the n terminal Gla end is chopped off
Definition
how is prothrombin converted to thrombin?
Term
10 gamma-carboxy-glutamyl residues (gla)
Definition
what is at the n-terminal region of prothrombin?
Term
serine proteases chymotrypsin and elastase
Definition
what are the 2 chains of thrombin??
Term
Ser, His, Asp
Definition
what is the catalytic triad?
Term
Arg-Gly bond in substrate (fibrinogen) -similar to trypsin
Definition
what bond is cleaved by thrombin?
Term
it is removed from circulation by the liver stimulating de novo synth of Gla proteins and secretion of these proteins into cirulation
Definition
what happens to activated prothrombin?
Term
1. I -> Ia
2. V -> Va
3. VII
4. VIII
5. XIII
Definition
what are the 5 major roles of thrombin? (things activated by it)
Term
acidic residues: Asp, Glu, tyrosine-o-sulfate
Definition
what are fibrinopeptides comprised of?
Term
half-staggered
Definition
what is the arrangement of fibrin monomers?
Term
cross linking of lys, and Gln catalyzed by factor XIIIa (transglutamidase)
Definition
what converts soft -> hard clots?
Term
isopeptide/pseudopeptide
Definition
what kind of bond forms between lys and glu?
Term
redox cofactor - catalyzes formation of Gla residues in blood clotting factors II, VII, IX, X and proteins C and S
Definition
what is the role of vitamin K in Gla proteins?
Term
II, VII, IX, X
Definition
what factors are bound by calcium?
Term
vitamin K dependent carboxylase
Definition
what enzyme converts glutamine to gamma-carboxyglutamate? (Glu->Gla)
Term
vit K epoxide and vit K reductase
Definition
what 2 enzymes participate in the 2 step reduction of vitamin K
Term
[image]
Definition
draw the vit K dependent carboxylase reaction
Term
dithiol dependent vit K epoxide reductase and vit K reductase
Definition
converts vit K epoxide back to Vit KH2
Term
it is a vit K analog that prevents clotting in vivo by inhibiting the reductases
Definition
what does warfarin/coumadin/dicoumarol do?
Term
thrombin/throbomodulin are activated, Va and VIIIa are inactivated
Definition
what activates protein C and S and what do they in turn inactivate?
Term
serine protease inhibitor ex: antithrombin III
Definition
what is a serpin?
Term
prevents clotting by assisting antithrombin III in binding to clotting factors, by a factor of about 9,000 for factor IIa, and 17,000 for Xa
Definition
what does heparan do?
Term
1. inactivation of Va and VIIIa by protein C
2. Inhibition of thrombin by antithrombin III
3. inhibition of extrinsic pathway by LACl
4. protein Z and ZPI
Definition
what are the 4 ways coagulation is regulated?
Term
lipoprotein associated coagulation inhibitor aka TF pathway inhibitor (TFPI) or anticonvertin. binds to TF-VIIa-Ca-Xa complex and inhibits factors VIIa and Xa
Definition
what is LACl
Term
ZPI + PZ = inhibits Xa
ZPI - PZ = inhibits XIa
Definition
What does ZPI (z dependent protease inhibitor) + or - Protein Z do?
Term
major form of hemophilia, facotr VIII deficient, x linked recessive
Definition
what is hemophilia A?
Term
minor form of hemophilia, x linked recessive, factor IX deficiency
Definition
what is hemophilia B?
Term
1. adhesion and aggregation at sites of vessel injury
2. phospholipid surface for binding clotting factors
Definition
2 main roles of platelets:
Term
subendothelial collagen
Definition
what do platelets adhere to?
Term
release of ADP and thromboxane A2
Definition
what promotes platelet aggregation?
Term
helps aggregation and forming the plug. binds to receptors GP Ib/IX, and GP IIb/IIIa
Definition
vWF's role in platelet aggregation
Term
bernard-soulier disease -GP Ib/IX
glanzmann's thromboastenia -GP IIb/IIIa
von Willebrand's disease - vWf
Definition
what are the 3 bleeding tendency diseases and what is deficient?
Term
fribrolysis via plasmin
TPA(tissue plasminogen activator) bound to fibrin converts plasminogen to plasmin, causing the fibrin clot to break into soluble fibrin fragments
Definition
how do blood clots dissolve?
Supporting users have an ad free experience!