Lecture 9 - Enzyme inhibitors Flashcards
(18 cards)
What are enzyme inhibitors
Molecules that interfere with enzyme catalysis, slowing or halting enzymatic transformations
What are the 2 classes of enzyme inhibitors
Reversible and irreversible
What are the classes of reversible enzyme inhibitors
Competitive
non competitive
un competitive
What is a competitive inhibitor
A competitive inhibitor competes with the substrate for the active site of the enzyme
The bound inhibitor does not inactivate the enzyme.
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What is KI
Inhibitor constant
indication of how potent an inhibitor is
What is a non-competitive inhibitor
binds to the free enzyme and the enzyme-substrate complex but at a different site to the substrate
The bound inhibitor does not inactivate the enzyme.
Non-competitive inhibition cannot be overcome by increasing [S]
What effect does non competitive inhibition have on KM and Vmax
The substrate affinity for the enzyme is unchanged so the KM remains the same
The inhibitor lowers the concentration of functional enzyme, so the Vmax is decreased (Vmax = k2[E]T).
What effect does competitive inhibition have on KM and Vmax
KM will be higher,
Vmax = unchanged
What is uncompetitive inhibition
An uncompetitive inhibitor binds at a site distinct from the substrate active site and binds only to the ES complex
The bound inhibitor does not inactivate the enzyme.
What effect does uncompetitive inhibition have upon KM and Vmax
An uncompetitive inhibitor lowers the maximum rate of catalysis, Vmax
The KM is lowered because the uncompetitive inhibitor increases the enzyme affinity for the substrate. This can be explained using Le Chatelier’s principle
What is irreversible enzyme inhibition
Irreversible inhibitors covalently modify a functional group on an enzyme that is essential for activity
How does irreversible inhibition work
Irreversible inhibitors covalently modify a functional group on an enzyme that is essential for activity
eg.
Diisopropylfluorophosphate (DIFP) inhibits all serine proteases and is a highly toxic sarin gas analogue
What are mechanism based irreversible inhibitors
hijack the normal enzyme reaction mechanism and can be selective to a single protease
How are enzymes regulated
Allosteric regulation
Reversible covalent modification
Proteolytic cleavage
feedback regulation
What is allosteric regulation
can bind to an enzyme resulting in activation or deactivation.
Binding is usually away from the active site but results in a change in the shape of the active site.
What is reversible covalent modification
Enzyme activity is modulated by covalent modification of amino acid residues in an enzyme molecule
Also known as a post-translational modification (PTM)
What is proteolytic cleavage
Enzymes regulated by proteolytic cleavage are produced in an inactive form called a zymogen or pro-enzyme
The enzyme becomes active after removal of a polypeptide segment by proteolytic cleavage
Specific cleavage causes conformational changes that form a fully functional enzyme active site
What is feedback regulation
The end-product of an enzymatic pathway inhibits an upstream enzyme to decrease rate of production
