Lecture 10 Flashcards
How can we increase a reaction rate:
- increase the temperature
- decrease the activation energy (G++)
Effect of an increase in temperature:
increase in tempearture will provide more kinetic energy to overcome the transition state
Effect of a decrease in activation energy:
increases the number of molecules that can achieve the transition state
Transition State (S++):
- particular chemical configuration of the substrate as it evolves toward becoming the product during reaction
- very short lived (transient) chemical state
- usually highest free energy peak of free energy diagram
Catalysts accelerates both the:
forward and reverse reactions
Enzymes decrease the transition state by:
binding the substrate and providing an environment that favors the formation of the transition state rather than the original form (S)
Transition state bound to an enzyme vs. the transition state free in solution:
a transition state tightly bound to the enzyme is at lower energy level than the transition state in free solution in an uncatalyzed reaction, primarily by decreasing enthalpy
Intermediate states of reactions:
catalysts can alter the reaction pathway to form an intermediate state that has a lower free energy than a transition state in an uncatalyzed reaction
Properties of the active site:
- 3D catalytic site/pocket
- multiple weak interactions between enzyme and substrate: hydrogen bonds, electrostatic itneractions, hydrophobic effects, and Van der Waals
- strong binding yet flexible
- small area in the enzyme
- non-polar environment
Lock-and-key model:
the active site of the enzyme fits the substrate as a lock does a key
Induced fit model:
both the enzyme and substrate are distorted on binding. The substrate is forced into a conformation approximating the transition state; the enzyme keeps the substrate under strain
Example of induced fit model:
Hexokinase catalyzes a glucose to glucose-6-phosphate reaction by folding domains toward each other
The key for highly specific binding of the substrate:
“breathing”
Function of enzymes:
- binds the substrate
- lowers the transition state energy
- directly promotes the catalytic events
Different ways enzymes enhance the rate of reactions:
- preferential binding to transition state through noncovalent interactions (enthalpy is more favorable)
- distortion of substrate or active site, promoting change to transition state (induced fit)
- binding of substrates to optimize proximity and orientation (makes entropy more favorable by decreasing the initial entropy of reactants)
- altering reaction pathway to include alternative intermediates (covalent catalysis)
- general acid-base catalysis (GABC) or metal ion catalysis
Charges can be stabilized by the active site of an enzyme:
- acid catalysis, H+ is donated by an amino acid in the active site to an atom that has a negative charge
- base removes H+ from an atom and develops a positive charge in transition state
Most common GABC catalysts:
His, Gly, Asp, Lys, and Arg
Function of lysozyme:
- defends against bacterial infection by cleaving peptidoglycan cell wall fo bacteria. Found in tears, saliva, and mucus; weakens the cell walls
- cleaves the D and E sites of an enzyme
Mechanism of lysozymes:
- glutamic acid is deprotonated, donating a H
- glutamic acid is protonated, accepting a H
- aspartic acid acts as a stabilizer
Function of Glu35:
- a general acid in the active site and then a general base to restore the enzyme to the original state
- adopts a protonated state because pH is 6.2
Function of Asp52:
acts as an electrostatic catalyst to form the transition state
Optimal pH of lysozyme activity:
pH 5, Glu35 is protonated and Asp is deprotonated
Example of chemical catalysis mechanisms:
protease chymotrypsin
Function of protease chymotrypsin:
- from the pancreas involved in protein digestion
- catalyzes the hydrolysis of peptide bonds proteins
- cleaves large amino acids like MPW
Mechanism of Chymotrypsin:
- S deprotonates F
- Histidine becomes a base and accepts proton from S
- S forms a covalent bond with F
- Histidine becomes an acid and donates proton to cleavage site
- Histidine acts as a base and gains proton from water
Chymotrypsin amino acids:
- Serine
- Histidine
- Aspartate
Function of Aspartate:
holds Histidine in correct formation for accepting H from Serine
Stabilization of tetrahedral intermediates by:
oxyanion hole
Function of oxyanion hole:
area of the active catalytic site that tightly binds tetrahedral transition state intermediates by forming hydrogen bonds between the peptide backbone of the enzyme and the oxygen atom dervied from the carbonyl group of the activated substrate;
also electrostatic interaction between oxyanion hole and oxyanion
Cofactors:
small molecules that enzymes need to execute biochemical reactions
Examples of cofactors:
coenzymes or metals
Apoenzyme + cofactor:
holoenzyme
Weakly bound coenzymes:
cosubstrates that associate or dissociate during reaction
Tightly bound coyenzymes:
prosthetic groups
Example of prosthetic:
zinc + alcohol dehydrogenase helps bind NAD+
Example of coenzyme:
niacin carries 2 electrons and 1 proton
Function of niacin:
accepts a hydride ion and converts alcohols to ketones or aldehydes
