Enzyme Classification and Reactions

Enzyme Classification

• Each enzyme is assigned a unique EC number based on its reaction type.
• First digit indicates the main class: oxidoreductase (1), transferase (2), etc.
• Second digit specifies the subclass of reaction.
• Third digit details the specific group transferred or bond cleaved.
• Fourth digit is the unique identifier within the sub-subclass.
• Example: ATP glucose phosphotransferase/hexokinase is EC 2.7.1.1 (transferase, phosphotransferase).

Enzyme Cofactors

• Cofactor: non-protein chemical component essential for enzyme activity.
• Metal ions (e.g., Fe²⁺, Mg²⁺, Mn²⁺, Zn²⁺) are important inorganic cofactors.
• Coenzymes: complex organic or metalloorganic compounds that assist enzymes.
• Prosthetic groups are tightly bound coenzymes or metal ions to enzymes.
• Holoenzyme: active enzyme with its cofactor; apoenzyme refers to the protein part minus its cofactor.

Enzymatic Activity

• Uncatalyzed reactions are typically slow under physiological conditions (neutral pH, mild temperature).
• Enzymes create a specific environment for reactions within the active site, a pocket in the enzyme.
• Active site's amino acid residues interact with substrates, forming an enzyme-substrate complex.

Enzyme-Catalyzed Reactions

• Catalysts increase reaction rates without altering equilibria.
• Ground state refers to the starting point of a reaction; ΔG° indicates standard free-energy change under specific conditions.
• Transition state represents the highest energy state along the reaction pathway, with ΔG‡ as the activation energy.
• Energy barriers need to be overcome for the conversion of substrate (S) to product (P).

Reaction Intermediates

• Reaction intermediates are species with finite lifetimes beyond molecular vibrations.
• ES (enzyme-substrate) and EP (enzyme-product) complexes are considered intermediates.
• The rate-limiting step in a reaction is often the highest energy point in the pathway.

Rate of Reaction

• Reaction rate is influenced by reactant concentrations and rate constants (k).
• For unimolecular reactions, V = k[S]; for bimolecular reactions, V = k[S1][S2].
• The Eyring-Polanyi equation relates rate constant k with activation energy ΔG‡, incorporating temperature and constants for Boltzmann (kB) and Planck (h).

Mechanism of Enzyme-Catalyzed Reactions

• Enzymes fit their substrates like a lock and key, being structurally complementary.
• These interactions may not allow substrates to reach the transition state effectively without aid from enzyme interactions.
• Enzyme must be complementary to the transition state to facilitate the reaction.

Rate Enhancements by Enzymes

• Enzymes enhance reaction rates by 5 to 17 orders of magnitude.
• Rearrangements of covalent bonds during reactions lower activation energy by creating alternative pathways.
• Non-covalent interactions stabilize the ES complex and contribute to catalytic efficiency.

Binding Energy and Reaction Specificity

• Enzymatic specificity arises from numerous weak interactions between enzyme and substrate.
• Enzymes can discriminate between substrates based on the strength and type of binding.
• Binding energy, released during substrate-enzyme interactions, is crucial in stabilizing the transition state.

Physical and Thermodynamic Factors

• Enzymes reduce the entropy of substrates, enhancing the likelihood of productive collisions.
• Proper alignment of enzyme functional groups is critical for catalytic activity.
• Induced fit: enzyme conforms to the substrate upon binding, facilitating reaction.
• Enzyme-substrate interactions often replace solvation shells formed by water, promoting effective catalysis.