C1.1 Enzymes & Metabolism

Define catalyst

A substance that speeds up chemical reactions without being used up or chemically altered

Define enzyme

A biological catalyst synthesised by living cells

Define activation energy

Minimum amount of energy needed to start a chemical reaction

Describe the role of enzymes, & how they carry it out

• Enzymes increase the rate of a specific biochemical reaction, that would otherwise be too slow to sustain life

• They do this by:

  • Converting substrates into products 

  • Lowering the activation energy → reactions occur more easily

Define metabolism

The sum of all chemical reactions in a living organism

What are the two types of metabolic reactions?

• Catabolic reactions - Involves the breaking down of molecules (e.g. respiration)

• Anabolic reactions - Involves building molecules (e.g. protein synthesis)

Describe how enzymes control reactions (5)

• Each reaction catalysed by a specific enzyme as their active site only fits certain substrates (enzyme specificity) 

• These enzymes regulate the reaction speed & direction:

  • Speed up/slow down parts of metabolism

  • Switch pathways on/off depending on conditions (e.g. exercise vs fasting) 

• Enzyme-controlled reactions form chains/cycles → product of one reaction becomes substrate for next

Describe anabolic reactions, & give examples (7)

Function: Builds larger molecules from smaller ones 

• Monomers + Energy → Macromolecule + Water

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Energy: Requires energy (endergonic)

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Examples:

• Condensation reactions where water is removed to join monomers & form macromolecules

  • Protein synthesis - joins amino acids to make polypeptides

  • Glycogen formation - joins glucose units for energy storage in animals

  • Photosynthesis - uses CO₂ and H₂O to build glucose 

Describe catabolic reactions, & give examples (7)

Function: Breaks down larger molecules into smaller ones

• Macromolecule + Water → Monomers + Energy

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Energy: Releases energy (exergonic)
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Example:

• Hydrolysis reactions where water is added to break bonds & provide raw materials/energy for cells

  • Digestion - breaks down proteins, carbs, fats, into monomers (e.g. amino acids, sugars, fatty acids)

  • Respiration - glucose is broken down to release ATP

What type of proteins are enzymes?

Globular proteins → compact & water-soluble nature

Explain what controls enzyme shape & its influence on catalysis (7)

• Their specific 3D conformation (tertiary structure) is formed by interactions between amino acids:

  • Hydrogen bonds

  • Ionic bonds 

  • Disulphide bridges  

  • Hydrophobic interactions

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Significance to catalysis:

• These interactions determine precise shape & chemical properties of the active site

• This maintains its function: bind substrate temporarily & lower activation energy

  • Enables chemical reaction to proceed faster w/o enzyme being depleted

What is the Induced-Fit model?

A revised model that suggests enzymes & substrates change shape slightly when they bind 

• This disproves the lock-and-key model that proposed a perfect fit

Describe the stages of Induced Fit

1. Approach - Substrate enter the enzyme’s active site

2. Conformational change - The enzyme’s active site molds itself around the substrate. The substrate may also change shape to fit more snugly.   

3. Catalysis - It puts strain on substrate bonds, making them easier to break/rearrange during the reaction

4. Release - After the reaction, products have different shapes & chemical properties, causing detachment from the active site. The enzyme reverts to original conformation, ready to bind another substrate. 

Why is induced fit significant?

1) Specificity - Ensures only the correct substrate can trigger conformational changes 

2) Efficiency - Weakening bonds lower activation energy for reactions

Explain the role of molecular motion (3)

1. Enzymes & substrates are constantly moving randomly in a fluid environment, allowing collisions to occur

2. Collisions must occur in the right orientation & with enough energy

3. A successful collision between the active site & substrate forms an enzyme–substrate complex

Describe factors affecting enzyme collisions (3)

1) Temperature - As temperature increases, molecules gain kinetic energy & move quicker = more frequent collisions

2) Concentration - Higher enzyme/substrate concentration = higher chance of collisions

3) Molecular size - Smaller molecules move faster = more frequent collisions

What happens to enzymes & substrates when movement is restricted?

• Sometimes, movement is restricted but reactions still occur: 

Immobilised substrates - Large molecules like DNA may be anchored in place so enzymes must move to them

Immobilized enzymes - Some enzymes are fixed to membranes so substrate must move to reach the enzyme’s active site

Define denaturation

Process by which an enzyme’s three-dimensional shape is permanently altered, leading to a loss of function

What are the causes of denaturation?

1) High temperatures 

2) Extreme pH 

3) Chemical agents (e.g. alcohol or heavy metals)

→ all disrupts/breaks bonds maintaining conformation

What are the effects of denaturation?

1. Active site changes shape

2. Substrate can’t bind properly 

3. Enzyme loses activity, often irreversibly → cannot lower activation energy & catalyse reaction

How do active sites maintain enzyme-substrate specificity?

Each active site has:

1) Shape that matches one substrate 

2) Amino acids w/ specific chemical properties (e.g. charge, hydrophobicity) 

• This allows precise interactions which maintain enzyme-substrate specificity

• Hence, enzymes will only catalyse one reaction / group of closely-related reactions

State factors rate of an enzyme-catalysed reaction depends on

1) How frequent enzyme & substrate molecules collide (collision theory)

2) Whether the enzyme’s active site remains functional (not denatured)

Describe the effect of temperature on enzyme activity

Temperature	Effect
Increasing temp	Molecules move faster, increasing collision frequency  → faster reaction
Optimum temp	Temperature where enzyme works most efficiently
Too hot	Active site changes shape → denaturation  Reaction slows & eventually stops

Describe the effect of pH on enzyme activity

pH	Effect
Optimum pH	pH where enzyme works most efficiently (often pH 7 for human enzymes)
Extreme pH	Too acidic/basic Disrupts hydrogen & ionic bonds in enzyme  Active site changes shape → denaturation

Describe the effect of substrate concentration on enzyme activity

Temperature	Effect
Low substrate	Fewer collisions → slower reaction
Increasing substrate	More frequent collisions → faster reaction
High substrate (enzyme saturation)	All active sites are occupied — reaction rate levels off

What does this graph represent? Describe its trend

The effect of temperature on enzyme activity:

1. Rises steeply

2. Peaks at optimum

3. Drops sharply due to denaturation

What does this graph represent? Describe its trend

The effect of pH on enzyme activity:

1. Rises steadily 

2. Peaks at optimum

3. Drops steadily

What does this graph represent? Describe its trend

The effect of substrate concentration on enzyme activity:

1. Rapid increase

2. Plateaus 

What factors is enzyme activity measured by?

1) Decrease in substrate concentration 

2) Increase in product concentration

What is the formula of rate of reaction?

Rate of reaction = Change in amount (substrate / product) ÷ Time taken

Give examples of enzyme-catalysed reactions & their measurement methods

Enzyme	Reaction	Measurement Method
Catalase	Hydrogen peroxide → Water + Oxygen	Measure volume of O₂ gas released
Amylase	Starch → Maltose	Iodine test: Stays orange-brown, not turning blue-black = starch digested
Lipase	Lipid → Fatty acids	pH indicator: solution becomes more acidic

How is the initial rate calculated?

1) Draw a tangent at steepest part of graph

2) Calculate gradient (product ÷ time taken)

Explain how enzymes change activation energy to catalyse reactions

• Enzymes lower activation energy (Ea) → reactions happen faster & more easily: 

  • Energy is used to break bonds in substrates (endergonic) to allow reaction to begin

  • Once reaction is complete, energy is released to form bonds in products (exergonic)

Where can enzyme-catalysed reactions occur?

• Inside cells = intracellular 

• Outside cells = extracellular

Describe intracellular enzyme reactions, & give examples

• These happen within the cell’s cytoplasm or organelles 

Examples:

Process	Location	Function
Glycolysis	Cytoplasm	Breaks glucose into pyruvate (first stage of respiration)
Krebs Cycle	Mitochondrial matrix	Produces ATP, CO₂, & other products in aerobic respiration

Describe extracellular enzyme reactions, & give an example

• These happen outside the cell, usually in the digestive system

Example: Chemical digestion in the gut 

Enzyme	Site of Action	Function
Amylase	Mouth & small intestine	Breaks down starch into maltose
Protease (e.g. pepsin, trypsin)	Stomach, small intestine	Breaks down proteins into amino acids
Lipase	Small intestine	Breaks down lipids into fatty acids & glycerol

Explain heat generation in metabolic reactions

• Metabolic reactions are never 100% efficient

  • Some energy from glucose, fats, & proteins is transferred to ATP

  • Inevitably, the rest is lost as heat energy (byproduct) 

Explain the importance of heat

Thermoregulation in endotherms (warm-blooded animals)

• Mammals & birds rely on metabolic heat to:

1) Maintain a constant internal body temperature

2) Function in cold environments 

3) Support enzymatic reactions, which work best at optimum temperature

Define metabolic pathway

A series of enzyme-catalysed chemical reactions in a cell

What are the types of metabolic pathways?

1) Linear 

2) Cyclical 

Describe linear pathways, & give an example (5)

• Straightforward process: substrates are converted into a final product via a series of steps, each catalysed by enzymes 

• The process does not loop back 

Example: Glycolysis 

• Occurs in cytoplasm

• Breaks glucose into two pyruvate molecules & net gain of 2 ATP + 2 NADH 

Describe cyclical pathways, & give examples (8)

• End products are fed back into first step → regenerating initial substrates 

• Continuous cycle as long as substrates & enzymes are available  
  

Examples: 

1) Krebs Cycle 

• Occurs in mitochondrial matrix

• Oxidising acetyl-CoA to synthesise ATP, NADH, FADH₂, CO₂

2) Calvin Cycle

• Occurs in chloroplast stroma

• Uses CO₂, ATP, NADPH to build glucose in photosynthesis

Define allosteric site

Any region on an enzyme that is not the active site

Describe the process of non-competitive inhibition

1. Specific molecules (called allosteric effectors) can bind to allosteric sites, usually non-competitive inhibitors

2. Binding causes a conformational change in the enzyme

3. This alters the active site’s shape → preventing substrate binding 

4. Even if substrate concentration increases, inhibitor’s effect remains → reducing/blocking enzyme catalysis

⭐ This binding is typically reversible 

Describe the process of competitive inhibition

1. Molecule w/ a similar shape to substrate fits into enzyme’s active site

2. While the inhibitor is bound, the real substrate cannot enter

3. No product is formed while the inhibitor occupies the site

⭐ The inhibition is reversible →  if inhibitor detaches, the substrate has another chance

Give an example of competitive inhibition

Statins 

• Drugs that competitively inhibit the enzyme HMG-CoA reductase, by blocking substrate binding 

  • Involved in cholesterol synthesis → reduces cholesterol levels in human body

Describe the differences between competitive & non-competitive inhibition

Feature	Competitive	Non-competitive
Inhibitor binding site	Active site	Allosteric site
Substrate competes?	✅	❌
Effect of high substrate concentration	Can overcome inhibition	Cannot overcome
Effect of low substrate concentration	Reduced rate of reaction

What is feedback inhibition?

A type of negative feedback used to regulate metabolic pathways

Describe the process of feedback inhibition

1. In a metabolic pathway, when enough of the end product is made, it binds to an enzyme that catalyzes an earlier step

2. This inhibits the enzyme’s activity, slowing or stopping the entire pathway

3. When the end product is used up, the inhibition lifts, & the pathway resumes

Describe an example of feedback inhibition (7)

Example: Isoleucine Biosynthesis

Substrate: Threonine

Product: Isoleucine

1. Isoleucine is an amino acid produced from threonine in a five-step metabolic pathway

2. When isoleucine builds up, it binds allosterically to the pathway’s first enzyme: threonine deaminase

3. This changes the enzyme’s shape, preventing threonine from binding to it 

4. As a result, no more isoleucine is made until the level drops again

Describe the strengths of feedback inhibition (3)

1) Prevents waste of resources and energy

2) Maintains homeostasis in the cell

3) Ensures balanced production of essential molecules

Describe the process of mechanism-based inhibition

1. An inhibitor binds to an enzyme’s active site

2. A chemical reaction takes place, permanently altering the enzyme

3. This causes the enzyme to be irreversibly inactivated & lose function

Give an example of mechanism-based inhibition, & how it works (6)

Penicillin

• Penicillin targets transpeptidase enzymes in bacteria

  • These enzymes help cross-link peptidoglycan → a key component in bacterial cell walls

How penicillin works:

1. Penicillin resembles the enzyme’s natural substrate, binding to the active site of transpeptidase

2. A chemical reaction forms a covalent bond with the enzyme

3. This permanently disables the enzyme, causing no cell wall formation

4. Due to lack of structural support, the bacterial cell bursts 

How is resistance to penicillin achieved? (2)

• Some bacteria evolve by altering their transpeptidase enzyme

• These altered enzymes (called penicillin-binding proteins) no longer allow penicillin to bind