Source: APK2105 Textbook, University of Florida
Difficulty: Intermediate Prerequisites: Chapter 2 notes (biomolecules, cell structure, especially carbohydrates and lipids). Familiarity with condensation and hydrolysis reactions is essential.
Chapter 3 is where the chemistry from Chapter 2 starts doing work. It covers the types of metabolic reactions (hydrolysis, condensation, phosphorylation, oxidation-reduction), the thermodynamic principles that govern whether reactions proceed forward or backward, and how enzymes control reaction rates. The chapter builds to the energy pathways: glycolysis and the Krebs cycle. This is the chapter students find most demanding in the first exam block, largely because it requires comfort with both chemistry and biology simultaneously. If you understand how enzymes work and how ATP is produced, the physiology chapters that follow will click into place.
Metabolism includes all chemical reactions in the body, divided into anabolism (building) and catabolism (breaking down). Reactions are governed by the law of mass action and require activation energy. Enzymes lower the activation energy barrier to speed reactions without being consumed. ATP is the body's energy currency, produced via substrate-level and oxidative phosphorylation. Glycolysis splits glucose into pyruvate (net gain: 2 ATP), and the Krebs cycle continues energy extraction after pyruvate is converted to acetyl CoA.
Metabolism
The sum of all chemical reactions occurring in the body. Includes anabolism (building larger molecules) and catabolism (breaking them down).
Anabolism
Metabolic reactions that build larger molecules from smaller ones. Requires energy input.
Catabolism
Metabolic reactions that break larger molecules into smaller ones. Releases energy.
Hydrolysis
A catabolic reaction where water is used to break a bond. One fragment receives a hydrogen atom, the other receives a hydroxyl group.
Condensation
An anabolic reaction where two molecules join and water is produced as a byproduct.
Phosphorylation
The addition of a phosphate group to a molecule, creating a phosphate bond. The most common example: adding a phosphate to ADP to form ATP (and water).
Dephosphorylation
The removal of a phosphate group from a molecule. Breaking down ATP to ADP + inorganic phosphate (Pi) releases energy.
Oxidation
A reaction that removes an electron from an atom or molecule. Always coupled with reduction.
Reduction
A reaction in which a molecule accepts an electron. Always coupled with oxidation. Think "OIL RIG" (oxidation is loss, reduction is gain).
Law of Mass Action
The principle that increasing the concentration of reactants relative to products drives a reaction forward, and increasing products relative to reactants drives it in reverse.
Equilibrium Constant (Keq)
A ratio describing where a reaction naturally settles.
Keq = 1: reactants and products are equal
Keq > 1: exergonic reaction, favours products (proceeds to the right)
Keq < 1: endergonic reaction, favours reactants (proceeds to the left)
Exergonic Reaction
A reaction that releases energy. Products have less energy than reactants. Equilibrium constant greater than 1.
Endergonic Reaction
A reaction that requires energy input. Products have more energy than reactants. Equilibrium constant less than 1.
Activation Energy
The additional energy molecules need to reach the transition state and react. The difference between the energy of the transition state and the energy of the reactants (or products).
Transition State
The high-energy, unstable intermediate form that molecules pass through during a reaction.
Activation Energy Barrier
The energy hurdle that must be overcome for a reaction to proceed. The potential energy of the transition state exceeds that of both reactants and products.
Enzyme
A specialised biomolecule (usually a protein) that acts as a catalyst, speeding up reactions by lowering the activation energy barrier. Enzymes are not consumed and can be reused.
Substrate
The reactant that binds to an enzyme's active site. The binding step is reversible and involves weak (non-covalent) bonds.
Active Site
The specific region on an enzyme where the substrate binds and the catalytic reaction occurs.
Affinity
The strength of interaction between a ligand (e.g. substrate) and a protein (e.g. enzyme). Higher affinity means tighter binding and faster reaction rates. Determined by shape and charge complementarity, not just size.
Saturation
The state in which all of an enzyme's active sites are occupied by substrate. Increasing substrate concentration beyond this point does not increase the reaction rate.
Cofactors
Non-protein components of an enzyme that are necessary for the enzyme to function.
Coenzymes
Molecules that participate directly in a reaction but do not themselves have catalytic activity. They carry electrons between reactions. Key examples: FAD, NAD, CoA.
Allosteric Regulation
Regulation of enzyme activity by a modulator binding to a regulatory site (not the active site). Reversibly changes the enzyme's shape and activity.
Covalent Regulation
Regulation of enzyme activity through covalent bonding of a chemical group (commonly a phosphate). Protein kinase catalyses phosphorylation of enzymes.
Feedback Inhibition
A regulatory mechanism where an enzyme in a metabolic pathway is inhibited by a downstream intermediate (product inhibits an earlier step).
Feedforward Activation
A regulatory mechanism where an enzyme is activated by an upstream intermediate (an early product speeds up a later step).
ATP (Adenosine Triphosphate)
The body's primary, temporary energy currency. Formed by phosphorylation of ADP. Synthesis is a condensation reaction requiring approximately 7 kcal.
Substrate-Level Phosphorylation
ATP production by direct transfer of a phosphate group from a metabolic intermediate to ADP.
Oxidative Phosphorylation
ATP production where ADP binds with free inorganic phosphate, driven by energy from the electron transport chain.
Glycolysis
The metabolic pathway that splits one glucose molecule (6 carbons) into two pyruvate molecules (3 carbons each). Occurs in the cytosol. Net yield: 2 ATP and 2 NADH per glucose. No oxygen required.
Krebs Cycle (Citric Acid Cycle)
The metabolic cycle that continues energy extraction after glycolysis. Pyruvate is first converted to acetyl CoA (the linking step), which then enters the cycle.
All metabolic reactions are bidirectional
Reactants enter the reaction; products come out
Key reaction types:
Hydrolysis: water breaks a bond (catabolic)
Condensation: two molecules join, water is produced (anabolic)
Phosphorylation: a phosphate group is added (e.g. ADP + Pi → ATP)
Dephosphorylation: a phosphate group is removed (e.g. ATP → ADP + Pi)
Oxidation: loss of an electron from a molecule
Reduction: gain of an electron by a molecule
Oxidation and reduction are always coupled (redox reactions). Central to energy metabolism.
As concentration of molecules increases, the energy of the solution increases
Equilibrium constant (Keq):
Keq = 1 → products and reactants are balanced
Keq > 1 → exergonic, reaction favours products
Keq < 1 → endergonic, reaction favours reactants
Increasing reactant concentration drives the reaction forward (to the right)
Increasing product concentration drives the reaction in reverse (to the left)
This is a core principle: the body manipulates concentrations to push reactions in the needed direction
The transition state is the high-energy intermediate form molecules must pass through
The activation energy barrier is the energy difference between the reactants and the transition state
Activation energy is the extra energy molecules need to reach the transition state
Lowering the barrier (e.g. with an enzyme) increases the reaction rate without changing the overall energy balance
Three main factors:
Reactant and product concentrations
Net rate = forward reaction rate minus reverse reaction rate
Shifting the concentration balance changes which direction dominates
Temperature
Higher temperature increases molecular movement, collisions, and therefore reaction rate
Height of the activation energy barrier
Lower barriers mean more molecules can reach the transition state
Net rate increases even though both forward and reverse reactions speed up
Enzymes are biological catalysts (usually proteins) that speed up reactions by lowering the activation energy barrier
They do not change the direction or overall energy of a reaction, only the rate
Mechanism:
Substrate binds to the enzyme's active site (binding step, reversible, always weak/non-covalent bonds)
Catalytic step occurs
Products are released; enzyme is unchanged and reusable
Substrate can sometimes dissociate before the catalytic step occurs
Enzymes are typically specific to one substrate type (substrate specificity), though exceptions exist (e.g. pepsin)
Catalytic rate: how many product molecules an enzyme generates per unit time
Substrate concentration: higher concentration → higher reaction rate, up to the point of saturation
Enzyme concentration: more enzyme molecules → more active sites available → faster rate
Affinity: how tightly the substrate binds to the active site. Higher affinity → higher rate. Determined by shape and charge complementarity
Temperature and pH: alter protein (enzyme) shape and therefore function. Extreme values denature enzymes
Cofactors: non-protein parts of an enzyme essential for function
Coenzymes: molecules that directly participate in the reaction without having catalytic activity themselves
Key coenzymes: FAD, NAD, CoA
Their main role: pick up electrons and shuttle them between different reactions
Allosteric regulation: a modulator binds to a regulatory site (not the active site), reversibly changing the enzyme's conformation and activity
Covalent regulation: a chemical group (often a phosphate) is covalently bonded to the enzyme, altering its activity. Protein kinase catalyses phosphorylation
Feedback inhibition: a downstream product inhibits an earlier enzyme in the pathway (prevents overproduction)
Feedforward activation: an upstream intermediate activates a later enzyme in the pathway (speeds up the chain)
ATP is the body's temporary energy storage molecule
Formed by phosphorylation of ADP (a condensation reaction)
Requires approximately 7 kcal to synthesise one ATP
Two production methods:
Substrate-level phosphorylation: a phosphate group is transferred directly from a metabolic intermediate to ADP
Oxidative phosphorylation: ADP combines with free inorganic phosphate, driven by energy from the electron transport chain
Occurs in the cytosol (no organelle required)
Splits one glucose molecule (6C) into two pyruvate molecules (3C each)
Energy balance per glucose:
2 ATP invested
4 ATP produced by substrate-level phosphorylation
Net gain: 2 ATP
2 NAD molecules are reduced to 2 NADH
No oxygen is consumed and no CO2 is released (anaerobic)
Before entering the Krebs cycle, pyruvate is converted to acetyl CoA (the linking step)
The Krebs cycle then extracts further energy from acetyl CoA
(Note: the source material covers only the linking step in detail; further Krebs cycle content may appear in subsequent chapters)
ATP synthesis: ADP + Pi → ATP + H2O (condensation, requires ~7 kcal)
ATP breakdown: ATP → ADP + Pi (releases energy)
Glycolysis net yield: 1 glucose → 2 pyruvate + 2 ATP (net) + 2 NADH
Redox coupling: Oxidation (electron loss) is always paired with Reduction (electron gain)
Equilibrium constant:
Keq > 1 → exergonic (energy-releasing)
Keq < 1 → endergonic (energy-requiring)
Keq = 1 → equilibrium
Glycolysis is the reason your muscles can produce energy in short, intense bursts even before your breathing rate increases. It does not require oxygen, which is why it provides the first few seconds of energy during a sprint.
Enzyme regulation (feedback inhibition, allosteric control) is the principle behind many drug designs. Statins, for example, inhibit an enzyme in the cholesterol synthesis pathway.
Students often think enzymes provide energy for a reaction. They do not. Enzymes lower the activation energy barrier, making it easier for existing energy to push the reaction through, but they do not add energy.
Oxidation does not always involve oxygen. It simply means losing an electron. The name is historical.
Students frequently mix up substrate-level and oxidative phosphorylation. Substrate-level phosphorylation transfers a phosphate directly from an intermediate to ADP. Oxidative phosphorylation uses energy from the electron transport chain.
Glycolysis does not require oxygen, but students sometimes assume all ATP production is aerobic. Glycolysis is entirely anaerobic.
⚠️ Be able to define and distinguish anabolism, catabolism, hydrolysis, condensation, phosphorylation, dephosphorylation, oxidation, and reduction. These terms appear throughout the rest of the course.
⚠️ The law of mass action and equilibrium constants are tested conceptually. Know what Keq > 1, = 1, and < 1 mean.
⚠️ Understand enzyme kinetics: what happens to reaction rate as you increase substrate concentration, enzyme concentration, or affinity. Know what saturation means.
⚠️ The four modes of enzyme regulation (allosteric, covalent, feedback inhibition, feedforward activation) are frequently examined. Be able to describe each with an example.
⚠️ Know the glycolysis energy balance cold: 2 ATP in, 4 ATP out, net 2 ATP, plus 2 NADH. No oxygen consumed.
⚠️ Understand the difference between substrate-level and oxidative phosphorylation.
True or False: Enzymes change the overall energy balance of a reaction.
Fill in the blank: The net ATP yield from glycolysis per glucose molecule is __________.
True or False: Oxidation and reduction reactions can occur independently of each other.
Fill in the blank: An enzyme that has all its active sites occupied by substrate is said to be __________.
True or False: Glycolysis requires oxygen.
Answers: 1. False (they only change the rate by lowering the activation energy barrier). 2. 2 ATP. 3. False (they are always coupled). 4. Saturated. 5. False (glycolysis is anaerobic).
Q: Explain the law of mass action and describe how it applies to metabolic reactions in the body.
A: The law of mass action states that increasing the concentration of reactants relative to products pushes a reaction forward, while increasing the concentration of products relative to reactants pushes it in reverse. The body exploits this by continuously removing products (e.g. consuming ATP as soon as it is made), which keeps the forward reaction favoured.
Q: Describe the mechanism of enzyme action, including what happens at each step.
A: The substrate binds to the enzyme's active site through weak, non-covalent bonds (the reversible binding step). The enzyme then catalyses the reaction (catalytic step), converting substrate to product. Products are released, and the enzyme is unchanged and ready to bind another substrate molecule. Sometimes the substrate dissociates before the catalytic step occurs.
Q: Compare allosteric regulation and covalent regulation of enzymes.
A: Allosteric regulation involves a modulator binding to a regulatory site (not the active site), reversibly changing the enzyme's conformation and activity. Covalent regulation involves a chemical group (often a phosphate) being covalently bonded to the enzyme, changing its activity. Phosphorylation by protein kinase is a common example of covalent regulation. Allosteric regulation is always reversible by modulator release; covalent regulation requires a separate enzyme to remove the chemical group.
Q: Walk through glycolysis, including the inputs, outputs, and where it occurs.
A: Glycolysis occurs in the cytosol. One glucose molecule (6 carbons) is split into two pyruvate molecules (3 carbons each). The process consumes 2 ATP but produces 4 ATP by substrate-level phosphorylation, yielding a net gain of 2 ATP. Two molecules of NAD are reduced to 2 NADH. No oxygen is consumed and no carbon dioxide is released.
Q: What is the difference between feedback inhibition and feedforward activation?
A: In feedback inhibition, an enzyme earlier in a metabolic pathway is inhibited by a product formed downstream. This prevents overproduction. In feedforward activation, an intermediate formed upstream in the pathway activates an enzyme further along, speeding up the pathway when its input increases.
The enzyme regulation concepts here (allosteric, covalent, feedback, feedforward) reappear throughout the endocrine and nervous system chapters. Hormones often work by activating or inhibiting enzymes.
Glycolysis and the Krebs cycle connect directly to later material on aerobic metabolism, the electron transport chain, and oxidative phosphorylation (where the bulk of ATP is actually produced).
Redox chemistry is foundational for understanding the electron transport chain and how mitochondria generate the majority of the cell's ATP.
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