Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Biochemistry > Biochem 2 M2 > Flashcards

Biochem 2 M2 Flashcards

(116 cards)

Start Studying
1
Q

Triad of Thrombosis

A
  • Increased coagulability of the blood
  • Abnormality in blood vessel wall structure
  • Change in Circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is FIIa

A

Thrombin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Steps of Hemostasis

A

1) Primary Hemostasis
2) Blood coagulation
3) Clot maturation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Primary Hemostasis

A
  • Platelet binds to damaged surface
  • Platelet aggregation
  • Vasoconstriction
  • Not that stable
  • Fast, seconds
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Blood Coagulation

A
  • Formation of Fibrin
  • More stable
  • Takes minutes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Clot Maturation

A
  • Covalent crosslinks
  • Very stable
  • Clot retraction
  • Hours / Days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

NETosis

A

Neutrophil release of extracellular traps (NETs) that binds infectious agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Thrombin

A
  • Serine Protease
  • Cleaves next to Arg (+Lys)
  • Regulated by Protein Cofactors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is Fibrin formed

A
  • Activation of Fibrinogen by Thrombin
  • Thrombin cleaves 4 peptide bonds
  • Arg-Gly bond at FpA & FpB at N-term.
  • New GRP formed at N-term.
    (Gly-Pro-Arg)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Fibrinogen Structure

A
  • 6 Polypeptide chains
  • 2 Alpha, 2 Beta, 2 Gamma
  • Covalently linked (26 disulfide)
  • All N-term. at center / E-region
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Fibrinogen Charges

A
  • Highly Negative (-25)
  • Mostly at FpA & FpB in E-region
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Formation of Fibrin Protofibrils

A
  • FpA cleavage shows HOLE
  • FpB cleavage shows KNOB
  • HOLE fits into KNOB
  • C-term. of a-chain form bridges bw protofibers (lateral dimension)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Formation of Fibrin Dimers

A

1) C-term. of y-chain interact with Ca+
2) Neutralization of Regions
3) H-Bonds formed b.w Tyrosine-Arginine & Arginine-Serine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Fibrinogen y’

A

Due to the alternative splicing of mRNA coding for y-chain
- 20 a.a longer
- Can lead to arterial Thrombosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Polymerization due to FpA & FpB

A
  • FpA: Linear Polymerization
  • FpB: Perpendicular Polymerization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

FXIII Structure

A
  • Tetramer
  • 2A (Megak, Monocy) + 2B (Liver) subunits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

FXIII Active site

A

Active site contains Cysteine (Sulfur)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

FXIII Lifespan

A
  • Very short
  • Eliminated by Ultrafiltration in Kidney
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Activation of FXIII

A

1) Thrombin cleaves activation proteins = FXIII’
2) Ca2+ initiates cleavage of B from the A’ subunit = FXIIIa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

FXIIIa Catalyzed reaction

A
  • Forms Iso-peptide bonds bw 2 y or a-chains
  • Initiates Cross-Linkage
  • Bw Lysine-Glutamine side chains
  • NH3 released (Ammonia)
  • Increases clot mech. stability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Rotational Thromboelastometry (ROTEM)

A
  • Info on overall efficiency of Blood Coagulation system
  • Based on detecting mech. strength of blood clots
  • Quick results, but no reason given
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

FXa

A
  • For Conversion of Prothrombin to Thrombin in 2 step process
  • 2 Hydrolytic steps
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Conversion of Prothrombin to Thrombin

A

1) FXa cleaves peptide bond next to Arg forming Meizothrombin
2) FXa catalyzes another hydrolytic step and forms Thrombin
3) Positive feedback of Thrombin can cleave second bond to form Th from MT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Prothrombin Structure

A
  • Catalytic Domain
  • Fragments 1 & 2
  • F1 & F2 serve as attachment to Phospholipids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Prothrombinase Complex makeup
- Phospholipid Membrane - FXa - protease - FVa - cofactor - FII - inactive prothrombin
26
Prothrombinase Function
- Conversion of Prothrombin to Thrombin - FVa is used as a Cofactor that Enhances the reaction of FXa - Increases rate by 300,000 fold
27
Tissue Factor
- Transmembrane Protein - Found in cells not normally exposed to blood - Binds to FVIIa - Acts on FX ---> FXa - Extrinsic Xase complex
28
TFPI
(Tissue Factor Pathway Inh.) - Produced by Endothelial cells in Liver - Made up of K1, K2, K3 - Cofactor S
29
TFPI Process
1) K2 binds FXa 2) K1 binds FVIIa 3) K3 binds Protein S cofactor for stability
30
TFPI Isoforms
- a: All 3 domains - B: No K3 domain (hemophilia)
31
Hemophilia Treatments
- TFPI Blockers - FVIII infusion - FVIIa infusion
32
Antithrombin
- Protease inhibitor (SERPIN) - Prevents spread of Thrombin from point of its formation by inactivation - 3400 nm
33
Heparin
- Polysaccharide - Highly negative (COO-, SO3-) - Accelerates inhibition of Thrombin - Allosteric activator of Antithrombin - Exposes reactive loop by HBS
34
Heparan Sulfate
- Same function as Heparin - Produced by body
35
Does Heparin work alone?
No Antithrombin is necessary for its function
36
a2-Macroglobulin
- Thrombin Inhibitor - Creates trap for Thrombin - Tetrameric Structure - Attracts thrombin to cleave peptide bonds - Produced by Liver
37
Protein C system effect
Destroys Prothrombinase complex
38
How is Protein C ativated
- Cleavage done by Thrombin - Mediated by Thrombomodulin binding to Th instead of fibrin
39
Protein C system Steps
1) Thrombin binds Thrombomodulin 2) Thrombomodulin activates Protein C 3) APC + Protein S inhibits FV & FVIIIa (Less clotting)
40
Thrombin Exosite 1 binds Fibrin
- Keeps making Fibrin from Fibrinogen - Activates FXIII for cross-linkage of fibrin - Strengthened clot
41
Thrombin Exosite 1 binds Thrombomodulin
- Activates Thrombomodulin - Protein C activation - Protein C System - Inhibited Clotting factors FV & FVIII
42
Where is Highest amount of TM found?
Capillaries
43
Does Meizothrombin have any effect on Protein C system?
Yes (93%) Meizothrombin can activate Thrombomodulin to activate Protein C leading to clotting inhibition
44
Gla Domains
- Found in Vitamin-K dependent proteins - Keeps factors attached to phospholipid membrane (y-carboxyglutamate domain)
45
Gla domain funtion
1) Gla binding sites bind Ca2+ 2) Hydrophobic group inserted into phospholipid layer 3) Anchors the Factors to the plasma membrane for efficient function
46
Vitamin K dependent Proteins
- II (Prothrombin) - VII - IX - X - Protein C & S
47
How is Gla domain formed
- Postranslational Modification of Glutamic Acid - Carboxylase in E.R of Liver adds carboxylic group to glutamic acid
48
How Vitamin K forms Gla
1) Vitamin K Hydroquinone needed as a cofactor + CO2 + O2 2) y-Carboxylase turns Glu to Gla 3) VK epoxide is formed (unusable) 4) VKOR (oxidoreductase) used to form VK hydroquinone and repeat
49
What blocks VKOR?
- Coumarins (Warfarin)
50
Indirect Anticoagulant Drugs
Do not bind the active site of Thrombin - Heparin (LMWH) - Vitamin-K antagonists - Fondapurinux
51
Direct Oral Anticoagulant Drugs
Inhibit Thrombin and FXa sites - Dabigatran - Rivaroxaban - Apixaban
52
How are DOAC drugs safe?
They do not affect FVIIa which still allows clot formation do to Extrinsic pathway by Tissue Factor
53
Plasminogen Structure
- Carboxy Terminal - Kirngle Domains (Produced by liver)
54
What can cause Plasminogen C-term. activation
Plasmin through Positive-Feedback
55
Plasminogen Kringle domain
Binds the plasminogen to Lysine residues on the Fibrin
56
Plasminogen Activation
- Activated to tPA or uPA - tPA + Plasminogen = Plasmin - Fibrin Cofactor
57
What a.a form Plasminogen Active site
- Serine - Histidine - Aspartate (Serine Protease)
58
tPA Inhibitor
Tissue Type Plasmin Activator - PAI-1 (release by endothelial cells)
59
Plasmin Inhibitor
a2-Antiplasmin
60
Plasminogen Activation by uPA
Urokinase - Inflamation - Produced by Monocytes, Neutrophils, Tumor cells, Endothelial cells. - uPA-R
61
What stimulates activation of uPA by uPA-R?
- Plasmin - Kallikrein Convert single chain (inactive) pro-uPA to Double chain (active) uPA
62
Endogenous Plasminogen Activators
- tPA - uPA - FXIIa
63
What anchors Plasminogen & tPA to PM?
- Annexin a2 - p11 (Ca2+)
64
Exogenous Plasminogen Activators
Proteins that bind either Plasminogen or Plasmin to break down Fibrin - Streprokinase (Plasminogen) - Staphylokinase (Plasmin)
65
Streptodornase
DNAase enzyme released by bacteria to break down NETs from Neutrophils
66
How is integrity of clot broken down?
Plasmin must cleave 3 peptide bonds in the same cross sectional plane of Fibrin
67
If Plasmin acts on Fibrinogen
- E Fragments - D Fragments
68
If Plasmin acts on Fibrin
- D-Dimers (iso-peptide bond) - E Fragments
69
Antifibrinolytic Agents
- Lysine (free) - e-amino caproic acid - Tranexamic acid
70
PAP Complex
- When Plasmin binds a2-antiplasmin - Irreversible (covalent) - Most aggressive Plasmin inhibitor
71
Role of FXIIIa in a2-antiplasmin
- Cross-links a2-antiplasmin in fibrin mesh - Embeds a2-antiplasmin into clot to inhibit plasmin action
72
Forms of a2-antiplasmin
- Meth (native) / 30% / Reduced stroke - Asp / 70% More methionine formed by Polymorphism where Arg swapped for Trp
73
TAFI
Thrombin Activable Fibrinolysis Inh. - Carboxypeptidase - Inactive precursor - Produced in Liver, Monocytes, Megakaryocytes - Removes Lys binding sites of tPA from Fibrin - Removes Plasminogen from fibrin
74
TAFI activation
- Once cleaved by Thrombin - Becomes Carboxypeptidase - Specificity towards Lys & Arg residues
75
Steps of Platelet function
1) Injury 2) Adhesion 3) Activation 4) Secretion and Aggregation
76
Adhesion Stage Platelets
1) Platelets recognize collagen (type-4) 2) Either bind directly or by specific receptors (GP-VI or VWF)
77
Activation Stage Platelets
Ca2+ released in platelet cytosol
78
Secretion & Aggregation Stage Platelets
1) Due to Ca2+ signal, Vesicle secretion 2) Exposure of cell surface receptor to mediate aggregation of platelets 3) Activated by Thromboxane-A & ADP
79
What Adhesion happens in Arteries
1) GP1ba binds VWF 2) Bridge between Collagen and Platelets (Catch Bond) 3) Strength of binding increases with more flow & shear stress
80
Von Willebrand Factor
- Produced in endothelium of Venules - Polymer of monomers (disulfide bridges) - The longer, the more adhesive - Catch Bond GPIba - Increases FVIII lifespan
81
What controls VWF length
ADAMTS13 - Cleaves VWF monomer to smaller pieces - >40 can attract platelets without damage
82
ADAMTS13 deficiency leads to
Thrombotic Thrombocytopenic purpura
83
GPIIbIIIa activation
1) ADP (TXA) provokes Ca2+ signal 2) PKC phosph. GDP to GTP 3) GTP attracts Talin and Kindlin 4) Receptor activates and binds Fibrinogen 5) Fibrinogen forms bridges bw 2 platelets = Aggregation
84
Vesicles released by activated Platelets
- Dense Body: ADP, Serotonin, Ca2+, Poly(Pi) - a-Granule: Proteins that support blood clotting (P-selectin, binding site for neut. NETosis)
85
PAR
Protease Activated Receptors - Thrombin activated - Irreversible - Platelet aggregation
86
Prostacyclin (PGI2) in Platelets
Potent antiplatelet agent - Higher cAMP - PKA act. - inh. aggregation
87
Why is Scramblase activated when Platelets activate?
It sends Negative PL to the outer PM layer, which allows for better attachment of clotting factors (Phosphatidylserine/inositol)
88
How does Aspirin work?
Inhibits COX, so no TxA formed. - COX-1: Platelets - COX-1/2: Endothelial cells
89
Effects of Clopidogrel
- Purinergic Receptor Antagonist - Blocks Platelet activation & aggregation by ADP
90
ectoADPase
- Hydrolyzes ADP - Opposes the platelet aggregating effect
91
Effects of NO on Platelets
1) NO from eNOS 2) sGC turns GTP to cGMP 3) cGMP activates PKG 4) PKG activates MLCP 5) Vasodilation (Anticoagulant)
92
cGMP / PDE3 effects
- cGMP inhibits PDE3 - Inh. causes Increased cAMP - More cAMP means less Ca2+ - Less platelet aggregation
93
S-Nitrosylation
NO attaches to S group on FXIII - Inh. of FXIII
94
Primary Cilium Mechanosensors
1) PC1 detects mechanical signal 2) PC2 causes Ca2+ influx as a result 3) Signal transduction and TFs (STAT6 & P100) 4) Can cause activation of eNOS
95
Ach-R
Pentamer 2a, 1B, 1y, 1d
96
Hydropathy plot
Allows the prediction of a Protein's TM topology
97
Open probability
The time an ion channel spends in the open state within a chose time period = total open time / total obs. time
98
Single Channel rate constants
Determine how many times the channel opens before inactivation
99
What happens to channels at Physiological ion concentrations
They reach theoretical limits of Throughput rates (since they are diffusion limited)
100
Can ion channels tell between same charged Ions
Yes Only the specific ion can go through due to Carbonyl Oxygens that mimics hydration shells of specific ions
101
Can a specific ion channel let another ion in in absence of its usual ion
No Na channel for Na+ only K channel for K+ only
102
VG-K channel
Tetramer with 6 TM domains and conserved P loop Extracellular selectivity filter (GYG)
103
Passage of K+ through its channel pore
Only 2 K+ found in pore at a time either in 1,3 or 2,4 conf. Separated by water in bw.
104
VG-Na channel
Monomer made up of 4 domains Asp. and Glu on P-loop
105
VG-Ca channel
Monomer made up of 4 domains 4 Glu on P-loop
106
What determines the selectivity of VG channels?
The conserved P-loop
107
X-ray crystallography
To determine 3D structure of Proteins (hard on ion channels since they are hydrophobic)
108
What provides the Gating charge in VG K+ channels?
Arg-Lys residues on Subunit 4
109
What treatment can stop inactivation of VG K+ channels? (+ Name)
Trypsin Cuts N-terminal peptide providing the "Ball & Chain" mechanism Called N-type inactivation
110
What do mutations in the VG K+ channels lead to?
Increased excitability e.g prolonged ventricular AP
111
Explain Inward rectification in ATP sensitive K+ channels
Large cations (e.g Mg2+) found in cytosol Plug outward K+ channels So more inward K+
112
Where do ATP and ADP bind on ATP sensitive K+ channel?
- ATP: KIR subunit (P-loop) - ADP: SUR subunit
113
VG-Cl channel
Homodimer in Skeletal Muscle to stabilize Em Mutations cause Myotonia (inability to relax)
114
CFTR Cl channel
Monomer ABC protein family Activated by PKA (cAMP) that phosphorylates 10 serines in regulatory domain
115
What did CFTR evolve from
Degradation of the inner gate of an active transporter
116
nACH-R
Pentamer Activated by 2 ligands binding Can be desensitized Mutations lead to Myasthenia/weakness

Biochemistry (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions