Session 11-Regulation of protein function Flashcards
What are isoenzymes?
Different forms of the same enzyme that have different kinetic properties
True or false: accumulation of the product of a reaction inhibits the forward reaction
TRUE
Give an example of product inhibition
Glucose-6-phosphate inhibits hexokinase activity
What relationship do allosteric enzymes show between rate and substrate concentration?
Sigmoidal, rather than rectangular hyperbola seen for simple enzymes
Complete the sentence:
Substrate binding to one subunit makes subsequent binding to other subunits progressively ______
Easier
What do allosteric activators do?
Increase the proportion of enzyme in the R state
What do allosteric inhibitors do?
Increase the proportion of enzyme in the T state
True or false: phosphofructokinase is not allosterically regulated
FALSE - it is and it sets the pace of glycolysis
What are the allosteric activators for phosphofructokinase? (2)
AMP
Fructose-2,6-bisphosphate
What are the allosteric inhibitors for phosphofructokinase? (3)
ATP
Citrate
H+
What do protein kinases do?
Transfer the terminal phosphate from ATP to the -OH group of Ser, Thr and Tyr
What do protein phosphatases do?
Reverse the effects of kinases by catalysing the hydrolytic removal of phosphoryl groups from proteins
Why is protein phosphorylation so effective? (5)
- Adds two negative charges
- A phosphoryl group can make H-bonds
- Rate of phosphorylation/dephosphorylation can be adjusted
- Links energy status of the cell to metabolism through ATP
- Allow for amplification effects
Complete the sentence:
When enzymes activate enzymes, the number of affected molecules _________ _____________ in an enzyme cascade
Increases geometrically
What does amplification of signals by kinase cascades allow?
Amplification of the initial signal by several orders of magnitude within a few milliseconds
What does it mean by “glycogen breakdown and synthesis are reciprocally regulated”?
The signals that stimulate glycogen breakdown also inhibit glycogen synthesis
Which enzyme catalyses glycogen breakdown?
Phosphorylase a
Which enzyme catalyses glycogen synthesis?
Glycogen synthase
How are many enzymes activated?
Specific proteolytic cleavage
How are digestive enzymes synthesised by specific proteolysis?
They are synthesised as zymogens in the stomach and pancreas
What are zymogens?
Inactive precursors - converted into an enzyme when activated by another enzyme
How is blood clotting mediated?
By a cascade of proteolytic activations that ensures a rapid and amplified response
How is apoptosis mediated?
By proteolytic enzymes, caspases, which are synthesised in an inactive form (procaspase)
What do endogenous inhibitors do?
Regulate protease activity
What binds to trypsin and stops its activity?
Pancreatic trypsin inhibitor
What is an example of a protein that inhibits a range of proteases?
Alpha1-antitrypsin
What are people with emphysema deficient in and what does this cause?
Alpha1-antitrypsin which leads to the destruction of alveolar walls by elastase
What are the two types of short term protein regulation?
- Substrate and product concentration
2. Change in enzyme conformation (allosteric regulation, covalent modification and proteolytic cleavage)
What are the two types of long term protein regulation?
- Change in rate of protein synthesis
2. Change in rate of protein degradation
What is an example of enzyme induction/repression?
Alcoholics make more alcohol dehydrogenase
Which enzyme catalyses the formation of a fibrin clot?
Thrombin
Why is the intrinsic pathway more important than the extrinsic pathway of blood clot formation?
Once it starts, it is self-sustaining
What are Gla domains?
Gamma-carboxyglutamate residues which are very negatively charged
What do Kringle domains do?
Keep prothrombin in the inactive form
How does Ca2+ play a role in blood clotting?
Interacts with damaged membranes and acts as a cross-bridge with Gla domains to allow for a quicker reaction
Complete the sentences:
The newly formed clot is stabilised by the formation of _____ bonds between the side chains of ______ and _________ residues in different monomers. This cross-linking reaction is catalysed by _________________ which is activated from _________________ by thrombin.
Amide Lysine Glutamine Transglutamine Protransglutaminase
What is classic haemophilia a defect in?
Factor VIII
What are two ways to stop the clotting process?
- Localisation of (pro)thrombin - dilution of clotting factors by blood flow and removal by liver
- Digestion by proteases
How is the clotting process regulated? (1)
Specific inhibitors - antithrombin III (AT3)
