Enzyme Catalysis ... Oversimplified picture of enzyme catalysis. Page 16. II.
Binding Energy in. Catalysis: • In most case, initial interaction is noncovalent.
Enzyme Catalysis thermodynamic aspects
k2 ES --> [EX*] --> EP --> E + P
Oversimplified picture of enzyme catalysis
II. Binding Energy in Catalysis: •
In most case, initial interaction is noncovalent (ES) making use of hydrogen bonding, electrostatic, hyodrophobic and van der Waals force to effect binding.
•
ES: Catalytic groups are now an integral part of the same molecule, the reaction of enzyme bound substrates will follow first order rather than second order kinetics.
E + S --> ES --> [EX*] --> EP --> E + P (weak)
II. Binding Energy in Catalysis: •
Change in free energy ΔGB. Favorable interaction between the enzyme and substrate result in a favorable intrinsic binding energy.
•
Entropy is lost when substrate binds to the enzyme. (a)Two entities become one. (b)Substrate is less able to rotate. (c)Substrate become more ordered.
•
Weak interactions between the enzyme and substrate are optimize and stabilize the transition state.
E + S --> ES --> [EX*] --> EP --> E + P (weak) (stronger)
Catalytic Strategies •
Catalysis by approximation – In reactions that include two substrates, the rate is enhanced by bringing the two substrates together in a proper oirentation.
•
Covalent catalysis – The active site contains a reactive group, usually a powerful nucleophile that become temporarily covalently modified in the course of catalysis.
•
General acid-base catalysis – A molecule other than water plays the role of a proton donor or acceptor.
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Metal ion catalysis – Metal ions can serve as electrophilic catalyst, stabilizing negative charge on a reaction intermediate.
Origin of the catalytic effect in enzymes We need to state the problem in a clear way: comparison to uncatalyzed reaction in water is essential
‡ water Fundamental question:
‡ ΔG
≠ ΔGwat
enzyme
≠ ΔGenz
transition state stabilization or
≠ ΔGcat
E+S
ground state destabilization EP
ES reaction coord.
E+P
Origin of the catalytic effect in enzymes
Hypotheses: • electrostatic stabilization • strain and distorsion • entropy: proximity and alignment • desolvation • quantum effects: tunnelling