Lecture 10 Flashcards
What are two primary ways to increase the rate constant?
– increase temperature and decrease the activation energy.
–This occurs because K is proportional to 1/e. Since increasing temperature decreases e and decreasing activation energy decreases e, a large K will be observed
What happens when enzymes decrease activation energy in terms of molecules?
since the barrier is less,
– lowered activation energy increases fraction of molecules that have enough energy to attain transition
True or false. Enzymes increase both the forward and reverse direction rates
True
How do enzymes work to make the transition state more favorable?
– it forms a more stable transition state by increasing the number of favorable interactions, thus lowering enthalpy of the transition state which is favorable
—> strong binding of transition state
(deltaHcat < deltaHnon)
–At the same time, it could increase the entropy of transition state to make the ordered fashion slightly more favorable
—> proximity and orientation favor formation of transition state. (deltaScat > deltaSnon)
How would enzymes increase the entropy difference between reactants and transitions states to make it more favorable?
– They basically force the reactants by binding them together , reducing their entropy. This reduced entropy in the reactants will make the unfavorable difference in entropy between reactants and transition state less, essentially making it more favorable.
True or false
Sometimes alternate pathways to the products can be induced by enzymes to lower activation energy, essentially changing chemical structures of catalyzed transition states
True
Who discovered the first model of enzyme substrate binding? How about the second?
Emil Fischer. Daniel Koshland
What is the current model of enzyme and substrate?
– enzymes and substrates exist in an induced fit mechanism where both substrate and enzyme change slightly upon interaction to maximize the increase in favorability of the reaction and also explaining the binding specificity of catalysis.
–During the induced binding, the substrate is forced into a configuration that better resembles its transition state
T or F, a transition state tightly bound to enzyme that is at lower energy level than transition state in free solution
True; enthalpy is decreasing
–> thus energy involved to adpt transition state is lower than without enzyme
True or false
catalytic pocket of enzyme is flexible and can change conformation before binding the substrate.
false. it changes conformation once the substrate binds that allows it to become sterically and chemically complementary to the substrate
What are characteristics of the active site in enzymes?
– small area in the enzyme that often is a nonpolar environment. Binding occurs via various multiple weak interactions.
What are the type of electrostatic catalysis interactions that can occur at the active site? What do they do?
- hydrogen bonds
- electrostatic interactions (ion)
- hydrophobic effects
- van der waals.
- they allow strong bindings yet flexibility to promote the formation of the transition state
true or false
metal ions can be in the active cite to participate in catalysis
True
Why might a nonpolar environment be favored in the active site of an enzyme?
since water may react to some degree with anything in the active site, having a nonpolar environment prevents undesirable hydrolysis reactions
What are the different ways enzymes enhance the rate of reactions? (6)
– preferential binding to transition state through noncovalent interactions (electrostatic catalysis, makes change in enthalpy more favorable)
– Distortion of substrate or active site, promoting change to transition state (induced fit)
– Binding of substrates to optimize proximity and orientation (makes change in entropy more favorable by decreasing initial entropy of reactants)
– altering reaction pathway to include alternative intermediate (occurs often in covalent catalysis)
– other mechanisms: General Acid-Base catalysis (GABC) or Metal Ion catalysis
What are non covalent bond stabilized catalysis often called?
electrostatic catalysis
true or false
covalent catalysis often includes alternative intermediates?
True
How are enthalpic stabilization of enzyme transition states generally occur?
– The transition state charges can be stabilized by residues present in the active site, decreasing enthalpy and making it more favorable
How does acid vs base catalysis generally work?
– acid catalysis will donate proton from its active site acidic residue to stabilize the negative charge on the substrate
– base catalysis removes an H+ from the transition state of the substrate that will remove any excess positive charge.
What are common GABC catalysis?
H, D, E K, and R
Where does cleavage occur on the sites on the lysozyme enzyme. What does it typically cleave?
– between the d and e site on the lysozyme cleavage occurs of sugar residues
– it cleaves the peptidoglycan cell wall of bacteria found in tears saliva and mucus
What are the specific sugar residues where the cleavage occurs on a lysozyme?
NAG-NAM
What is the general mechanism of the lysozyme action?
– a protonated Glu 35 acts as a proton donor in the first part of the cleavage.
– The Asp52 acts as a stabilizer of positive charge via covalent interactions and the NAG leaves.
– In the secondary step Glu 35 acts as a proton acceptor and Asp52 remains as a charge stabilizer because the second intermediate has a positive charge.
After this final step, the original Nam is regenerated
What is different about the E AA in lysozyme compared to a typical E AA?
The pka is elevated to a 6.2 to its ionizable side chain that is typically around 4 (3.9). This allows it to remain protonated in the optimal pH of 5 in the lysozyme.
