Lecture 11: Enzymes II- Catalysis Flashcards
What do enzymes do?
- Lower activation rate
2. Stabilize the transition state
What DON’T enzymes do?
- Change the Delta G (Enthalpy/Free energy) of the reaction
2. Irreversibly change shape
Catalyst
Increases rate (speed) of a reaction, but does not undergo any permanent chemical change as a result
How do we speed up reaction/ overcome ACTIVATION BARRIER?
- Increased the energy of all molecules by increasing the temp (however proteins can be denatured)
- Lower the energy barrier by DECREASING the energy of the transition state**
Induced Fit Model
When substrate binds, the enzyme changes shape so that the substrate is forced into the transition state
How is catalysis achieved?
- Substrate orientation
- Straining substrate bonds
- Creating a favorable microenvironment
- Covalent and/or non-covalent interactions between enzyme and substrate
Catalysis Strategy #1- Covalent Catalysis
Enzyme covalently binds to the transition state (electrons transfer)
Catalysis Strategy #2- Acid-Base Catalysis
Partial proton transfer to the substrate
Catalysis Strategy #3- Approximation
For e/p’s to be exchanged, they must be in proper spatial orientation and close contact (proximity) for the reactant molecules must occur
–> If molecules held together in proper orientation, they are likely to interact = CALLED ENTROPY REDUCTION
If entropy (S) increases then
G (energy) increases always!
Catalysis Strategy #4- Electrostatic Catalysis
Stabilization of unfavorable changes on the transition state by polarizable side chains in the enzyme and/or metal ions
**Active site for Serine Proteases/Chymotrypsin
Catalytic triad and oxyanion hole
**Active site for Carbonic Anyhdrases
3 His + Zn++ - OH
**Specificity for Serine Proteases/Chymotrypsin
Hydrophobic specificity pocket
**Specificity for Carbonic Anhydrases
(Size of entryway)
Why do we need proteases?
Recycling
Regulation (remove from circulation)
Defense (chew it up)
At the active site of Chymotrypsin (called catalytic triad)
Serine= nucleophile
Histidine=a base (proton acceptor)
Aspartic Acid= an acid (proton donor)
Papain (human cysteine proteases)
Calpains and caspases
(Require Ca2+ as cofactor, apoptosis, split active site residues over a heterodimer)
-Found in Euks, Eubacteria, but not Archea
HIV Protease
Aspartyl protease;
- Cleave precursor proteins
- Homodimer with 1 active site Asp per subunit
Example of HIV protease
Renin;
Secreted by kidneys, helps increase BP and retain water/salt
Cysteine proteases
Papain and caspases
Aspartyl proteases
HIV protease and renin
Metalloproteases
Thermolysin, MMP’s, ADH
Thermolysin
- Active site is His-His-Glu with Zn and another Glu holds H2o
- Secreted from Gram bacteria
