AH L1 - The Origins of Enzyme Catalytic Rate Enhancement Flashcards
What are enzymes made of and what do they do?
Proteins.
Catalyses nearly all chemical reactions in living organisms.
Are all enzymes made of proteins?
No - catalytic RNA eg hammerhead ribozyme
How much do enzymes accelerate reactions by factors of?
10^6 to 10^7
How have the 3D structures of enzymes been solved ?
X-ray crystallography & cryoelectron microscopy.
Why is it important to study enzymes?
- Essential for cellular function.
- Targets for drug action.
- Used in biotech industries.
What are some enzyme drug targets?
- G - protein-coupled receptors.
- Ligand-gated ion channels
- Voltage-gates ion channels
- Nuclear hormone receptors.
- **Catalytic Receptors
- Kinases
- Proteases**
- Transporters
- Other enzymes
What is this symbol ‡? What does it mean?
Double Dagger.
Preferential stabilization of the transition state.
What is the equation for the non-catalysed reaction?
S <-> P
S= ground state at start = substrate
P = ground state at end = product
What is the formula for an enzyme catalysed reaction?
E + S <-> E.S <-> E.P <-> E + P
What does delta G mean?
the change in free energy
What do enzymes do to ∆G^‡?
It reduces it so that effects the rate at which chemical equilibrium is obtained.
What is ∆G⌄B?
Intrinsic binding energy - refers to the total interaction energy btwn the transition state and enzyme functional groups.
What is a major source of free energy used by enzymes?
Intrinsic binding energy.
What does ∆G⌄B show between the enzyme and transition state?
Favourable interactions i.e. favourable intrinsic binding energy.
What thermodynamic factors does intrinsic binding energy (∆G⌄B) need to overcome?
- Loss of entropy of molecules in solution.
- Desolvation (removal of solvent from a material in solution) on binding of substrate(s).
- Distortion of substrates that occurs in many reactions.
- Alignment of catalytic functional groups on the enzyme.
Are enzymes inefficient?
No they are highly efficient. can increase activity by several 10-folds.
What happens with every 10-fold increase in relative rate enhancement (kcat/kuncat)?
The transition state of the reaction (‡) must be stabilised by 5.7 kJ/mol relative to ‡ of the uncatalyzed reaction.
What chemical mechanisms are there for catalysis? (They do this to achieve satbilisation)
- The proximity (Approximation) effect
- Electrostatic catalysis
- Acid-base catalysis
- Covalent (nucleophilic) catalysis
What is the proximity/ approximation effect?
Proximity effect, is to organize the substrates within the active site of the enzyme such that the reactants are much closer together than they would be in a typical solution. Enhancing the proximity of reactants increases their collision frequency, thus causing the reaction to proceed at a faster rate.
What is the effective concentration (effective molarity)?
The ratio of the 1st-order rate constant of an intramolecular reaction involving two functional groups w/in the same molecular entity to the 2nd-order rate constant of an analogous intramolecular elementary reaction.
This ratio has the dimensions of concentration.
What happens are you decrease the rotational and translational entropy of a molecule?
The relative rate (kcat) and effective molarity (M) increase.
What is electrostatic catalysis?
Electrostatic catalysis occurs when the enzyme active site stabilizes the transition state of the reaction by forming electrostatic interactions with the substrate. The electrostatic interactions can be ionic, ionic-dipole, dipole-dipole, or hydrophobic interactions.
