Lecture 13: Introduction To Enzyme Function Flashcards
What is an enzyme?
Enzymes are proteins.
They catalyse the conversion of substrates (S) to products (P).
Like all catalysts they are chemically unchanged at the end of the reaction.
Enzymes do not change the equilibrium position of the reaction.
Folding into a specific 3-D conformation is important for activity.
Two models of catalysis:
‘Lock and Key’.
‘Induced Fit’.
Most enzymes use both strategies. ‘Induced Fit’ is particularly important for multi-substrate enzymes.
Chemical Catalysis Of Enzyme Reactions
Substrates and reacting groups are held close together.
Reacting groups are orientating correctly with respect to each other.
Reacting bonds are often stretched or bent (resembles transition state).
Active sites are usually rich in hydrophobic residues.
- Can change pKa of charged amino-acid side-chains and substrate groups.
Bulk solvent is excluded from enzyme active sites;
- charged groups are not masked.
Ordered water molecules often participate in the reaction.
Protons can be donated or accepted by active site groups (acid/base catalysis).
Nucleophilic catalysis (acyl-enzyme intermediates).
Enzymes are usually stereospecific (chiral environment).
Enzymes often use cofactors (metal ions e.g., Mg2+) and cosubstrates (often nucleotides e.g., ATP). These are derived from vitamins and minerals.
Enzyme active sites are often complementary to transition states – distortion of bond lengths and bond angles.
The smaller the degree of freedom, the higher the rate.
Acyl-substitution reactions
Step 1: Activation of active site nucleophile by deprotonation.
Step 2: Acyl substitution using active site nucleophile.
Step 3: Acyl substitution by water to regenerate enzyme.
Typical enzymes using this type of mechanism:
Serine Proteases (Chymotrypsin, trypsin, elastase etc.).
Cysteine Proteases (Papain).
Penicillinases and other β-lactamases.
Lipases.
Esterases and thioesterases.
