Chemical Reaction Rates

Chemical Reactions

• A chemical reaction involves the production of at least one new molecule through a chemical change.
• The rate of a chemical reaction is determined by how quickly reactant molecules are consumed or product molecules are produced.

Factors Affecting Reaction Rates

• The physical nature of reactants affects reaction rate (solid, liquid, or gas).
• Smaller particle sizes of reactants lead to increased reaction rates.
• Higher temperatures increase reaction rates.
• Increased concentrations of reactants lead to increased reaction rates.
• Catalysts increase reaction rates.

Free Energy of Activation

• Every chemical reaction has a specific activation energy or energy threshold to be reached before a reaction occurs.
• The Free Energy of Activation (ΔG‡) describes this.
• It is the minimum energy required to form the transition state.
• The Free Energy of Activation (ΔG‡) determines the rate (speed) of the reaction: high activation energy equals a low/slower reaction rate, while low activation energy equals a high/faster reaction rate.
• The reactants need to form a transition state, an intermediate chemical stage between reactant and product.
• Only reactant molecules that possess enough energy to exceed the Free Energy of Activation, and pass through the transition state, proceed to products.

Catalyst Definition

• Catalyst is a chemical that increases the rate of a chemical reaction by providing an alternative mechanism with a lower activation energy. These can be inorganic, organic, or biological macromolecule.
• It is not consumed or permanently altered
• Catalysts don't alter the fundamental nature of the reaction (e.g., equilibrium or free energy)
• Enzymes are biological (protein) catalysts enhance the velocity of chemical reactions without being altered

Catalysts and Equilibrium

• Catalysts increase both forward and reverse reaction rates, leaving the equilibrium unaltered.

Enzymes as Catalysts

• Enzymes are catalysts with similar characteristics to inorganic catalysts
• Enzymes are mostly proteins, that catalyse and control almost all chemical reactions in and around cells

Enzyme Reaction Rate

• Enzymes greatly enhance reaction rates, sometimes by a factor of trillions
• Chemical reactions within living organisms rarely occur in the absence of enzymes
• Enzymes speed up reactions that would otherwise occur too slowly for life to exist

Enzyme Nomenclature

• Most enzymes are globular proteins
• Enzyme names usually end in -ase, -me, or -in.
  • Example: carboxypeptidase, lysozyme, and chymotrypsin
• Enzymes are classified by function and have official numbers.

Enzyme Classification by Function

• Oxidoreductases: Involved in redox reactions.
• Transferases: Facilitate group transfer.
• Hydrolases: Catalyse hydrolytic reactions.
• Lyases: Responsible for additions to double bonds.
• Isomerases: Catalyse isomerisation.
• Ligases: Catalyse condensation of two molecules.

Oxidoreductases

• H+ acceptors/donors (eg NAD, NADP, FAD) include succinate dehydrogenase

Transferases

• Transfer of functional groups from one molecule to another
• Hexokinase is one
• Transaminases are another

Isomerases

• Cause interconversions of optical, geometric, or positional isomers (intramolecular rearrangement)
• Phosphohexose isomerase, converts Glucose-6-Phosphate to Fructose-6-Phosphate

Enzyme Structure

• Unconjugated enzymes don't need other factors to function.
• Conjugated enzymes require a cofactor:
• Cofactors may be non-protein, organic (coenzymes like vitamins), or inorganic (Fe2+, Mg2+).
• Tightly bound cofactors are called prosthetic groups (e.g., heme).
• Holoenzyme (active) = enzyme + cofactor
• Apoenzyme (inactive) = enzyme - cofactor

Co-enzymes

• Coenzymes are organic, usually vitamins
• They serve as acceptors or donors for functional groups
• Examples: ATP in phosphorylation and NAD+ in redox reactions
• Co-enzymes are required for:
• Oxidoreduction, group transfer and isomerisation reactions
• Reactions forming covalent bonds.

Co-enzyme Physiological importance

• Effectively a second substrate
• They counterbalance effects in substrate, for example if substrate is oxidised, co-enzyme is reduced
• Needed for physiological importance as energy transfer and Glycolysis

Enzymes - Substrates

• One or more molecules specifically recognised by an enzyme in an enzyme-catalysed reaction.
• Transformed to a product.

How Enzymes Speed Up Reactions

• Enzymes, like other catalysts, speed up reactions.
• Enzymes increase reaction rates up to 10^20 over uncatalysed reactions
• Provide an alternative route with a lower free energy of activation.
• Non-enzyme catalysts for chemical reactions can increase rates from 10^2 - 10^4.
• Enzyme activity is the rate at which an enzyme catalyses a reaction.

Enzyme Characteristics

• Increases reaction rate
• High affinity and specificity for substrates
• High capacity for regulation (more detail in subsequent units)

Affinity and Specificity

• Affinity is the total strength of binding between a substrate and the enzyme's active site
• Specificity is the 3D spatial 'fit' of a substrate within the active site.
• High affinity generally leads to high specificity.
• Use dissociation constant (Kd) to describe the affinity between a ligand (L) and a protein (P) – in this case an enzyme
• Michaelis constant (Km) used when studying enzyme-substrate interactions (more detail in next lecture).
• A low Kd, or Km, indicates a strong interaction whilst a high Kd, or Km, indicates a weak interaction.

Enzyme Specificity Details

• Specificity is achieved through conformational precision in the binding interaction between the substrate molecule(s) and the residues in the active site of the enzyme
• Binding pockets have complementary shapes, charge and hydrophilic/hydrophobic characteristics to the substrates
• The number and types of interactions between the substrate molecule and residues in the active site are dependants
• More interactions = greater specificity

Enzyme Range of Specificities

• Exhibit a range of specificities
• Absolute specificity: catalyses only one reaction using particular substrates
• Broad specificities: catalyses reactions using substrates with a similar structure to the most specific substrate (eg; alcohol dehydrogenase)
• Stereochemical specificity: catalyses reactions involving only one stereochemical form

Importance of the parts of the the protein molecule

• Parts of the protein not involved in the active site provide a framework that:
• Can regulate enzyme activity, especially if it contains other sites that activators and inhibitors can bind.
• Can interact with other proteins.
• Activate enzyme and they are bigger as pro-enzymes, protected by a removed cap
  • Example: trypsinogen to trypsin in intestine
• Protect active site, to conserve an enzyme and stop it from 'side reactions' especially with water