Enzymes and Chemical Reactions

Enzymes

• An enzyme is a protein that has catalytic properties
• These properties are due to the power of specific activation

Chemical Reactions

• Chemical reactions require an initial energy input, known as activation energy
• During a reaction, molecules exist in a transition state

Reaction Pathway

• Free energy is the energy available in a chemical reaction to do useful work
• Reactants are the initial substances that participate in a chemical reaction
• The activation energy is required for reactants to reach the transition state, which then leads to the formation of products
• Products are the substances formed as a result of a chemical reaction
• The reaction coordinate represents the progress of the reaction from reactants to products

Making Reactions Faster

• Increasing temperature accelerates molecular movement
• Biological systems are sensitive to temperature fluctuations
• Enzymes increase reaction rates without raising the temperature
• Enzymes lower the activation energy
• Enzymes create a new, faster reaction pathway
• Enzyme-controlled reactions occur much faster than non-enzymatic reactions, between 10^8 to 10^11 times faster

Enzyme Structure

• Enzymes are proteins
• Enzymes have a globular shape
• Enzymes possess a complex 3-D structure
• Human pancreatic amylase is an example of an enzyme

The Active Site

• The active site is a crucial part of an enzyme
• The shape and chemical environment of the active site facilitates chemical reactions

Cofactors

• Cofactors are non-protein molecules that assist some enzymes
• Tightly bound cofactors are termed prosthetic groups
• Coenzymes are cofactors that easily bind and are released
• Many vitamins function as coenzymes
• Nitrogenase enzyme with Fe, Mo and ADP cofactors example

The Substrate

• The substrate are the reactants activated by the enzyme
• Enzymes exhibit specificity for their substrates
• The active site determines the specificity

The Lock and Key Hypothesis

• The substrate and the active site of the enzyme fit precisely together
• An enzyme interacting with a substrate is analogous to a key fitting into a lock
• A temporary enzyme-substrate complex forms
• The products formed have a different shape than the substrate
• Once products form, they are released from the active site
• Enzymes can attach to another substrate after product release

The Lock and Key Hypothesis Function

• Enzyme specificity is explained by the Lock and Key model
• Loss of enzyme activity upon denaturation is also explained by this model

The Induced Fit Hypothesis

• Proteins can change their shape or conformation
• Substrate binding induces a conformational change in the enzyme
• The active site molds into a precise conformation
• This active site moulding makes the chemical environment suitable for the reaction
• Substrate bonds stretch to lower activation energy

The Induced Fit Hypothesis Explained

• The induced fit explains enzymes that can react with a range of similar substrates
• Example: Hexokinase (a) without (b) with glucose substrate

Factors Affecting Enzymes

• Substrate concentration, pH, temperature, and inhibitors influence enzyme activity

Substrate Concentration: Non-enzymic Reactions

• Reaction velocity increases proportionally with substrate concentration

Substrate Concentration: Enzymic Reactions

• Reaction velocity increases rapidly but plateaus at a saturation point when all enzyme molecules are occupied
• Altering enzyme concentration changes the maximum velocity (Vmax)

The effect of pH

• Optimal pH values allow enzyme activity

The Effect of pH on enzymes

• Extreme pH levels cause denaturation
• It changes enzyme structure
• It distorts the active site, preventing substrate binding
• Small pH changes near the optimum alter charges, changing enzyme and substrate molecules
• Ionization affects substrate binding

The Effect of Temperature on enzymes

• Q10 is the temperature coefficient which represents the increase in reaction rate for every 10°C rise
• For chemical reactions, Q10 equals 2 to 3
• Enzyme-controlled reactions follow this rule as they are chemical reactions
• High temperatures denature proteins
• Optimal temperature balances Q10 and denaturation
• Most enzymes have an optimum temperature around 30°C
• Cold-water fish enzymes denature at 30°C
• Certain bacteria have enzymes that can withstand up to 100°C
• Most enzymes fully denature at 70°C

Inhibitors

• Chemicals reducing enzymatic reaction rates are inhibitors
• Inhibitors are usually specific and act at low concentrations
• They block, but generally don't destroy, the enzyme
• Drugs and poisons often act as enzyme inhibitors in the nervous system

The effect of enzyme inhibition

• Irreversible inhibitors combine irreversibly with amino acids at the active site
• Examples include nerve gases and organophosphorus pesticides, which act on acetylcholine esterase

The effect of enzyme inhibition (Continued)

• Reversible inhibitors can be removed by dialysis
• There are two categories of reversible inhibitors

The effect of enzyme inhibition (Types of Reversible Inhibitors)

• Competitive inhibitors compete for the active site
• The inhibitor's action is proportional to concentration
• Competitive Inhibitors resemble the substrate's structure

The effect of enzyme inhibition

• Non-competitive inhibitors bind at sites other than the active site, not influenced by the substrate concentration
• Example: Cyanide combines with iron in cytochrome oxidase
• Heavy metals like Ag or Hg combine with -SH groups and can be removed by chelating agents like EDTA

Applications of inhibitors

• Negative feedback is the end product inhibition
• Poisons such as snake venom, plant alkaloids, and nerve gases all have inhibitors
• Medicines such as antibiotics, sulphonamides, sedatives, and stimulants all have inhibitors