Enzyme Catalysis

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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.



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