Mechanisms Inhibitors Flashcards
What is a ternary complex
A complex where the enzyme is attached to two substrates
E (s1)(s2)
What are bimolecular reactions
A + B turns into C + D
What are sequential reactions
The reaction where a terinary complex is formed (e and the two substrates) then two products are released
In the cleland representation of a bimolecular reaction in which ways can the substrates bind to the enzyme
Either ordered (a binds first then B) or random (B then A)
What are double displacement reactions
Also called ping pong reactions,
They are bi molecular reactions where a substituted enzyme intermediate is formed
Ex. The enzyme produces product c
First and turns into E-x (intermediate) then makes product d
Meaning 1 or more products a first released before all of the reactants bind to the enzyme
What are calatylic strategies
Enzymes use one or more of these strategies to catalyze a reaction and facilitate formation of the transition state
What are the four calatylic strategies
Covalent catalysis
General acid base catalysis
Metal ion catalysis
Catalysis by approximation and orientation
What is covalent catalysis
The active site of the enzyme has a reactive group that becomes covalemtly modified during catalysis
Ex. The oh side chain of serine bonds to the substrate covalently to make the acyl enzyme
What is general acid base catalysis
A molecule (not water) plays the role of a proton acceptor (general base) or a proton donor (general acid)
Ex. His 57 acts as a base and accept a proton from ser 195s OH group to make it a better nucleophile
What is metal ion catalysis
The metal ions help by:
Generating a nucleophile by increasing the acidity of a nearby molecule like water (ex. Zinc making water deprotonated itself)
Increasing the binding energy through interaction with the substrate
Stabilizing the negative charge on a reaction intermediate (to make reaction go faster)
What are the two catalytic strategies in invertase enzyme
What type of bimolecular reaction is it
Covalent catalysis and general acid base catalysis
Double displacement
What is catalysis by approximation and orientation
The two substrates first bound to an enzyme then are brought close to each other and out in the correct orientation
Ex. A-ppp is close to ap
This makes one of the p easily switch to the app to make 2 ADP
What are inibitors
Small molecules that bind to enzymes and inhibit their activity
Exist in nature as toxins or poisons or are made by chemists
In terms of binding to the enzyme they can be reversible or irreversible
What are reversible inhibitors
They bind to and dissociate from the enzyme quickly
There are three types and they differ based on how the inhibitor interacts with the enzyme
What are the three types of reversible enzyme inhibitors
Competitive
Uncompetitive
Non competitive
What are competitive inhibitors
The inhibitor looks like the substrate and binds to the active site
As the concentration of the inhibitor increases we need higher concentration of the substrate to get a certain velocity
The inhibitor has no effect on Vmax (reaches Vmax after longer time) but it increases Km
What is uncompetitive inhibitition
The inhibitor binds to the enzymes substrate complex (the inhibitor is on the enzymes and this is bound there as well)
This causes an ESI (enzyme substrate inhibitor complex) where now product is formed
Both km (k1 goes up since ES complex is made) and Vmax decrease which causes parallel lines on the burk graph
What are non competitive inhibitors
Inhibitor binds to a spot on the enzyme other than the active site when there’s no substrate in it, or to the enzyme substrate complex
This means both the ESI complex and the EI complex don’t make any product
Vmax decreases and Km is same (because inhibitor doesn’t affect binding of substrate)
What are irreversible inhibitors
They’re either covenlently bound of very tight non covalenty bound to the enzyme
They’re use in experiments to determine the mechanism of the enzyme
What are the types of irreversible inhibitors
- Group specific reagent
- Affinity label
- Transition state analog
4 suicide inhibitor
What is a Group specific reagent
It modifies the r group of a specific amino acid
It’s only specific for the one r group on the enzyme, not specific for entire enzymes
What are affinity labels
Structurally similar to the substrate so they bind to a specific enzyme (not just aa residue)
They covelently modify AA residues of the enzymes active site
What are transition state analogs
They inhibit an enzyme by binding to the enzymes active site and mimicking the transition state
Natural tradition states are short live and unstable, but the analog is very stable.
So They bind even more tight to the active site than the actual intermediate
What are suicide inhibitors
A chemically modified substrate that binds and is initially processed by the enzyme
The catalysis process of it leads to a chemically reactive intermediate that inactivates the enzyme
This is because the covalent modification of the enzyme (substrate binding to it) causes the enzyme to become inactive and terminates any other reactions
