Principles of the coagulation cascade Flashcards

1
Q

Define coagulation?

A

Series of protein conversions that lead to fibrin formation

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2
Q

What does fibrin form?

A

Network of fibres that trap blood cells & proteins to prevent bleeding

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3
Q

What are the protein conversions mediated by?

A

Proteases cleave peptide bonds in proteins at specific sites eg. thrombin

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4
Q

What is fibrin’s signal?

A

Exposure of tissue factor

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5
Q

What is the structure of thrombin?

A

Catalytic triad containing the AAS histidine, asparagine & serine

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6
Q

What are exosites I and II required for?

A

specific recognition of the correct substrates

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7
Q

What aas of fibrinogen are key for binding to proteases?

A

Phe
Val
Arg (especially Arg - involved in all targets of thrombin)

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7
Q

What peptide bond is the site of catalytic cleavage?

A

Bond between Arg and Gly

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8
Q

What are the 3 steps of catalytic cutting between thrombin & fibrinogen?

A

Fibrinopeptide A -> Fibrin monomer -> fibrin network

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9
Q

What do EGF and Kringle domains mediate?

A

Protein/protein interactions & are involved in substrate binding

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10
Q

What do Gla domains mediate?

A

Membrane binding & serve as cofactors and/or substrate binding sites

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11
Q

What type of bond links the protease to the rest of the protein?

A

A disulphide bond

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12
Q

What happens if you remove calcium?

A

Clotting stops

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13
Q

What structure on cell membranes do clotting factors need to assemble into functional complexes?

A

-vely charged phospholipids found on activated platelets

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14
Q

Where do all Gla-domain clotting factors get carboxylated?

A

On glutamate residues

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15
Q

What do Gla domains bind?

A

Ca2+ ions

16
Q

What does carboxylation result in?

A

additional -ve charges which are required for membrane bind

17
Q

What is carboxylase?

A

Liver enzyme that depends on cofactor vit. K

18
Q

What absorbs vitamin K from our diet?

A

Bile salts from the liver

19
Q

What enzyme regenerates used, oxidized vitamin K?

A

Vitamin K epoxide reductase (VKOR)

20
Q

What can VKOR be blocked?

A

By vitamin K antagonists (warfarin)

21
Q

What happens if vitamin K is depleted?

A

Reduced Gla residues -> loss of coagulation factor function -> reduced clotting

22
Q

What is the result of thrombin cleaving off small peptides from fibrinogen?

A

Generates the fibrin monomer by uncovering polymerization sites (knobs A & B)

23
Q

What does fibrin polymerization involve?

A

Knob-hole interactions (knob A binds hole a, know B binds hole b)

24
Q

What are Ca2+ used for in the fibrin polymer?

A

Stability

25
Q

What are 4 properties of fibrin clots?

A

Elastic
highly extensible
viscous
stiffens in response to shear, tension or compression

26
Q

What are 5 factors that affect fibrin formation?

A

Thrombin conc.
blood flow
clot retraction by platelets
incorporation of other plasma proteins
degree of crosslinking by factor FXIII

27
Q

Which factor stabilizes the fibrin netwrok?

A

Factor XIII (plasma transglutamase) -> links side chains