protein function- basics/clotting

Question 1

Name the short term controls on enzyme activity

Answer 1

substrate and produce concentration

change in enzyme conformation

Question 2

Allosteric regulators are…

list properties

Answer 2

multi subunit
2 conformations–> tense / relaxed
follow sigmoidal kinetics
can be activators or inhibitors

Question 3

Name activators of phosphofructokinase

Answer 3

AMP

fructose-2,6- bisphosphate

Question 4

Name inhibitors of phosphofructokinase

Answer 4

ATP
Citrate
H

Question 5

What enzyme phosphorylate

Answer 5

kinases

Question 6

What enzyme dephosphorylate

Answer 6

phosphatases

Question 7

What is a zymogen

Answer 7

inactive form of an enzyme

Question 8

What is role of alpha 1 anti trypsin

Answer 8

inhibits range of proteases

deficiency allows destruction of alveolar walls by elastase

Question 9

Name two long term regulation

Answer 9

change rate of protein synthesis- enzyme induction or repression
change in rate of protein degradation- ubiquitin protease pathway

Question 10

outline intrinsic pathway of clotting cascade

Answer 10

damage to endothelial cells 
FXI 
FIX 
FVIII 
FX 
Fv
thrombin 
fibrin

Question 11

outline extrinsic pathway of clotting cascade

Answer 11

trauma releases Tissue factor  FIII 
FVII 
FX
FV
Thrombin 
fibrin

Question 12

What factor do pathways converge ?

Answer 12

FX

Question 13

What are the two key co factors?

Answer 13

FVIII

FV

Question 14

What factor responsible for positive feedback?

Answer 14

FXIII

Question 15

Describe the structure if prothrombin

Answer 15

serine protease C terminal
2 Kringle domains
carboxyglutamate domain

Question 16

What is the role of the kringle domains

Answer 16

keep serine protease inactive

Question 17

What is the role of the Gla domain

Answer 17

target it to appropriate site for activation

Question 18

How is gla domain formed?

Answer 18

PTM in liver add COOH to glutamate

Question 19

Describe the structure of fibrinogen

Answer 19

2 sets of tripeptides alpha beta gamma
3 globular domains linked by rods
n terminal regions of alpha and beta chains very negatively charged preventing aggregation

Question 20

Describe process of clot formation

Answer 20

thrombin cleaves fibrinopeptides A + B from central globular domain of fibrinogen
globular domains at c terminal of beta and gamma interact with exposed sequences at n terminal of cleaved beta and alpha
clot forms
clot stabilised by cross links by formation of amide bonds

Question 21

what enzyme is responsible is formation of crosslinks

Answer 21

transglutaminase activated by thrombin

Question 22

What is haemophilia a caused by

Answer 22

missing/ reduced FVIII

Question 23

How is the clotting process stopped

Answer 23

localisation of prothrombin - diluted by blood flow
digestion of factors by protein C
specific inhibitors e.g. antithrombin III (AT 3)

Question 24

What activates protein C

Answer 24

thrombin binding to thrombomodulin receptor on endothelial cell

Question 25

What causes fibrinolysis

Answer 25

t- plasmin activator (t-PA)
Streptokinase ( exogenous clot buster)
plasminogen to plasmin
plasmin to fibrin fragments