Enzyme Catalysis and Inhibition

Group Transfer

-Nucleophilic attack by the enzyme

-Enhanced electrophilicity of E-S covalent intermediate

-Elimination of the enzyme

Result: transfer of a functional group from one molecule to another

catalyst

-speeds up the rate of a chemical reaction

-regenerated

-changes the path of the reaction

Enzymes are...

proteins that function as catalysts

active site

The part of an enzyme or antibody where the chemical reaction occurs.

Natural substrates for enzymes

The reactant that an enzyme acts on

enzyme-substrate complex

A temporary complex formed when an enzyme binds to its substrate molecule(s).

enzyme catalysis

the increase in the rate of a chemical reaction by the active site of a protein

alternate reaction pathway with a lower energy barrier

enzyme can repeat reaction many times

enzyme is regenerated

5 enzymatic strategies

1. General Acid Base Catalysis

2. Approximation

3. Stabilizing charge of the TS

4. Distortion

5. Group Transfer

general acid-base catalysis

Catalysis in which a molecule other than water plays the role of a proton donor or acceptor.

Catalytic Triad

Ser, His, Asp

Approximation Catalysis

the reaction rate of the enhanced by bringing two substrates into close proximity (near each other)

overcomes the negative entropy

Distortion in Enzyme Catalysis

• Substrates do not fit the binding site

• Substrate distorts during binding

• Distorted conformation ≈ transition state conformation

Induced Fit Model of enzyme action

Change in the shape of an enzyme's active site that enhances the fit between the active site and its substrate(s)

components of enzyme-catalyzed reaction

substrate, enzyme, enzyme-substrate complex, product + enzyme molecule

Enzyme-product complex

The intermediate structure in which product molecules are bound to an enzyme molecule.

Valley on Rxn Profile Diagram

Enzyme-Substrate Transition State

The transition state in the reaction (bond-making & breaking in progress

bound to an enzyme

Peak on Rxn Profile Diagram

To catalyze a reaction, the Activation barrier (TS) must

TS must be stabilized lowering the Ea

enzyme inhibitors

substrate imposters that bind the active site

transition state

a high-energy intermediate state of the reactants where the bonds are being broken and bonds are being formed

transition state analogs

synthesized compounds that mimic the form of the transition state of an enzyme reaction

inhibitors of the enzyme because they bind more tightly to the enzyme than substrate

transition state analogs must match_________ & _________ of the ES Complex TS

geometry and stereoeletronics

specificity of enzymes

The ability of an enzyme to choose the exact substrate from a group of similar chemical molecules.

competitive inhibition

substance that resembles the normal substrate (transition state) and competes with the substrate for the active site

suicide substrates

molecules used to bind to an enzyme irreversibly and inactivate it

Denaturation

-A process in which a protein unravels, losing its specific structure and hence function; can be caused by changes in pH or salt concentration or by high temperature.

-Non-specific

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