lecture 19 Flashcards
in normal situations does the Km change?
no, only the Vmax can be increased by adding more enzyme concentration.
What does a low Km mean?
This reflects a high affinity of the enzyme for the substrate
What does a high Km mean?
This means that their is a low affinity of the enzyme for the substrate
What are the two kinds of reversible inhibition?
competitive and non-competitive
bind non-covalently
What is a competitive inhibitor?
is a structural analog of the substrate that competes
with the substrate for the binding to the active site of
the enzyme.
Example of a competitive inhibitor?
statin drug that competitively inhibits HMG CoA reductase which is the regulated enzyme of cholesterol synthesis.
how does a competitive inhibitor impact the M-M graph?
It increases the Km, but does not impact the Vmax
How does a non-competitive inhibitor impact the M-M graph
Does not change the Km but decreases the Vmax
How is the lineweaver-burk different from the M-M graph?
- It is a straight line…. instead of a hyperbolic curve
- dont need as many data points (less money)
- Vmax is mathematically obtained, instead of estimated
Why are some inhibitors irreversible?
The drug or poison will bind covalently to the enzyme
how to reverse irreversible inhibitors
The enzyme must be degraded and a new enzyme must be made
What leads to irreversible inhibition?
- modification of the active site
- blocking the sulfhydryl-group enzyme
- interfere with metal cofactor
Explain DFP (di-isopropyl flourophosphate)
it is an irreversible inhibitor of acetylcholinesterase
What symptoms does DFP poisoning have?
It leads to an accumulation of acetylcholine thus:
- blurred vision
- bronchoconstriction
- seizures
- respiratory arrest and death
How does DFP inhibit acetylcholinesterase?
The poison blocks a specific serine that forms normally a covalent bond with the acetyl group during catalysis.
What kind of inhibitor is aspirin?
irreversible inhibitor
What does aspirin inhibit?
COX-1 and COX-2
cyclooxygenase enzyme
What is aspirin used for?
300-500 mg pain relief
81 mg for reduced blood clotting
How is COX involved in blood clotting?
Thromboxane and prostacycin are involved in blood clotting
Throm- more blood clotting
prosta- less blood clotting
What does a low dose of aspirin do exactly?
It inhibits the COX genes in both epithelial cells and platelets
platelets cannot synthesize new COX, thus less thromboxane is made
What are suicide inhibitor drugs?
the enzyme itself changes the structure of the drug resulting in an irreversible inhibitor
What is an example of a suicide inhibitor drug?
Allopurinol
What does allopurinol do?
Xanthine oxidase uses the drug allopurinol instead of hypoxanthine as substrate and forms the irreversible inhibitor drug alloxanthine.
Alloxanthine (oxypurinol) binds irreversibly to the active site of xanthine oxidase and reduces the formation of uric acid
What does allopurinol treat?
Gout
