Enzyme Catalysis Mechanisms

Mechanism of Enzyme Catalytic Strategies

• There are four common mechanisms by which enzymes alter the active site to create the enzyme-substrate complex: covalent catalysis, general acid-base catalysis, catalysis by approximation, and metal ion catalysis.

Covalent Catalysis

• Occurs when one or multiple amino acids in the active site transiently form a covalent bond with the substrate.
• Forms an intermediate through a nucleophilic attack of the catalytic residues, which helps stabilize later transition states.

General Acid-Base Catalysis

• Takes place when a molecule other than water acts as a proton donor or acceptor.
• Water can be one of the proton donors or acceptors in the reaction, but it cannot be the only one.
• Amino acid side chains can act as general proton donors and acceptors in the active site of an enzyme.

Catalysis by Approximation

• Happens when two different substrates work together in the active site to form the enzyme-substrate complex.
• A common example involves water entering the active site to donate or receive a proton after a substrate has already bound.

Metal Ion Catalysis

• Involves the participation of a metal ion at the active site of the enzyme.
• Helps make the attacking residue a better nucleophile and stabilize any negative charge in the active site.

Allosteric Modulation

• Enzymes can be either a single subunit or comprised of multiple subunits.
• The subunits in a multisubunit enzyme can work together in a mechanism called cooperativity, which can either boost or inhibit enzyme activity.

Cooperativity

• Can result in either a T-state (tense state) or an R-state (relaxed state) of the enzyme.
• T-state has less affinity for binding substrate, while R-state has higher affinity and increased substrate binding.

Two-State Allosteric Model

• The concerted model states that when an enzyme is in the T-state, if one subunit changes to the R-state, then all of the other subunits will change to the R-state at the same time.
• The sequential model states that once one effector binds to one of the subunits, the rest of the subunit's affinity for the effector increases, but they all do not necessarily change from one state to the other.

Classification of Enzymes

• According to the International Union of Biochemists (IUB), enzymes are divided into six functional classes based on the type of reaction they catalyze.
• The six kinds of enzymes are: hydrolases, oxidoreductases, lyases, transferases, ligases, and isomerases.

Types of Enzymes

• Oxidoreductases: catalyze oxidation and reduction reactions.
• Transferases: catalyze the transfer of a chemical group from one to another compound.
• Hydrolases: catalyze the hydrolysis of a bond.
• Lyases: catalyze the breakage of bonds without catalysis.
• Isomerases: catalyze the formation of an isomer of a compound.
• Ligases: catalyze the association of two molecules.

The Role of the Active Site

• There are three different models of substrate binding to the active site of an enzyme: the lock and key model, the induced-fit model, and the conformational-selection model.
• The lock and key model proposes that the shape and chemistry of the substrate are complementary to the shape and chemistry of the active site on the enzyme.