Term
| Extrinsic Apoptotic pathway |
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Definition
Death receptors / Activators:
FasR(CD95) - FasL
TNFR1 - TNF -a
activation -> Fadd binding(adapter)
Fadd cleaves pro-caspase-8 to 3,6,7
(effector caspases)3,6,7 -> apoptosis |
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Term
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Definition
Cyt-C + Bax released from mitochondria
Cyt-c binds to APaf-1. Oligomerizes into
apoptosome
apoptosome: cleaves pro-caspase 9
Caspase 9 cleaves 3,6,9
CAD(Caspase induced DNase) ,activated by caspase-3, goes to nucleus and fragments DNA |
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Term
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Definition
Inhibitor of apoptosis proteins inhibit
effector caspases 3,6,7.
Smac/Diablo inhibit IAPs.
BID links extrinsic to intrinsic
pathways. Caspase activates BID |
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Term
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Definition
Anti-apoptotic:
BCL-2, BCL-xL block release of cyc C
(block Bax and Bak)
Proapoptotic:
Bax and Bak form pore
Bad,Bim(inhibit BCL-2, BCL-xL)
(anti-apoptotic proteins) |
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Term
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Definition
P53 trancriptionally activates
pro-apoptotics(BAX) by localizing to
nucleus
Directly effects by moving to
mitochondria and facilitating Bax
self-dimerization
(P53 binds to Bcl-xL, releases Bax)
p53 Inhibits anti-apoptotic genes
Bcl-2, Bcl-xl |
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Term
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Definition
Pl3K -> AKT(PKB) activates BCL-2(by
phosphorylating BAD)
Inhibits apoptosis.
PTEN inhibits action of PL3-kinase and AKT. (increases Apoptosis)
Pten mutated in Prostate cancer.
Increase in PSA: overactive Androgen
receptor signalling |
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Term
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Definition
Activated by binding collagen(binds
receptors), and thrombin(cleaves
receptors),fibrinogen, expose
phosphatidyl serine.
change shape and release granules.
Dense Bodies:
serotonin(vasoconstrictor)
Alpha Granules:
Vonwillebrand factor
Fibrinogen |
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Term
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Definition
Adhesion of platelets to subendothelial layer.
Binding of GP1B to collagen via vWF
Interaction between membrane
glycoproteins and sub endothelium |
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Term
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Definition
GPIIB/GPIIIA(Integrins) bind finbrinogen
Fibrinogen forms bridge between
platelets |
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Term
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Definition
Glanzmanns thrombasthenia: Severe
bleeding due to mutations in GP
Plavix interferes with GPIIB/GPIIIA
/Fibrinogen platelet aggregation |
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Term
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Definition
Thromboxane A2(platelet activation)
Phospholipid -> arachidonic acid ->
thromboxane A2.
Cycloxygenase is a key enzyme in
pathway. Target of aspirin |
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Term
| von Willebrand Factor(vWF) |
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Definition
vWF: contains binding sites for GP1B,
collagen, and factor VII
Adhesion of platelets(collagen) to vessel wall
Functionality due to higher molecular
weight of multimeric forms |
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Term
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Definition
Inherited deficiency in vWF
Most common congenital bleeding disorder
vWF deficiency results in defective
platelet adhesion |
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Term
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Definition
Factors synthesized in liver and secreted
in Zymogen(inactive) form.
Most enzymes involved are serine
proteases
ca+ ions required for most steps
Thrombin cleave and activates Factor VIII and Factor V.(positive feedback) |
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Term
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Definition
Factor Viia is not active without tissue
factor.
Tissue Factor + Factor VII -> TF:VLLA
TF:VLLA + factor X -> Factor Xa |
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Term
| Inhibition of coagulation by thrombomodulin |
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Definition
Thrombin + thrombomodulin. Activates APC
APC destroys factors Va and VIIIa
Inhibits coagulation cascade |
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Term
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Definition
In european population
Mutation in Factor V gene causes it to be resistant to APC. Arg -> Gln
Increased Risk of deep vein thrombosis |
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Term
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Definition
Factor VIII = Haemophillia A
Usually do to flip inversion
(intrachromosomal recombination)
Factor IX(hemophilia) B |
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Term
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Definition
Fibrin composed of Aa, Bb, and y chains
organized into Dimer
N-terminal ends highly negatively
charged and through repulsion prevent
aggregation
Thrombin releases fibrin peptide A and B
and clot is formed.
Factor XIIIa stabilizes the fibrin clot |
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Term
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Definition
Antithrombin: Serpin
(serine protease inhibitor)
Targets Factor Xa and thrombin
Antithrombin is stimulated by heparin
Give heparin to break up a clot |
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Term
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Definition
Fibrin clots degraded by plasmin
Plasmin circulates as plasminogen
Activated by tPA and uPA(serine
proteases) |
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Term
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Definition
Coumadin(warfarin) antagonize Vitamin K
Depresses vitamin K-dependent carboxylation of:
Prothrombin, proteins C and S,
Factors 7,9,10 |
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