Unit 6: Metabolism

1. Thermodynamics and its Application in Biological Systems

Metabolism refers to the sum of all chemical reactions that occur within a living organism to maintain life. These reactions are divided into two categories:

• Catabolism: The breakdown of complex molecules into simpler ones, releasing energy (e.g., cellular respiration).
• Anabolism: The synthesis of complex molecules from simpler ones, requiring energy input (e.g., protein synthesis).

Bioenergetics is the study of how energy flows through living systems, and it is governed by the laws of thermodynamics.

1.1 The Laws of Thermodynamics

First Law of Thermodynamics (Law of Conservation of Energy)

• Principle: Energy can be transferred and transformed, but it cannot be created or destroyed.
• Biological Application: Living organisms are energy transformers. For example, during photosynthesis, plants convert light energy into chemical energy stored in the bonds of glucose. During cellular respiration, organisms convert that chemical energy into a usable form, ATP (adenosine triphosphate), and release some energy as heat. The total amount of energy in the system (organism + surroundings) remains constant.

Second Law of Thermodynamics (Law of Entropy)

• Principle: Every energy transfer or transformation increases the entropy (disorder or randomness) of the universe. Spontaneous processes are those that increase the overall entropy.
• Biological Application: Living organisms are highly ordered, low-entropy systems. This seems to violate the second law, but it does not. Organisms are open systems, meaning they exchange energy and matter with their surroundings. To maintain their internal order, organisms must constantly take in energy from the environment. In the process of using this energy, they increase the entropy of their surroundings by releasing less ordered molecules (like CO₂ and H₂O) and heat.
  • Example: The breakdown of a single, complex glucose molecule into multiple, simpler CO₂ and H₂O molecules increases the overall entropy of the system and its surroundings.

1.2 Gibbs Free Energy (G)

Gibbs Free Energy (G) is the portion of a system's energy that can perform work when temperature and pressure are uniform throughout the system, as in a living cell. It is the most critical variable for predicting whether a biological reaction will occur spontaneously.

The change in free energy (ΔG) during a reaction is given by the equation:

ΔG = ΔH - TΔS

Where:

• ΔG: Change in Gibbs Free Energy. The sign of ΔG determines if a reaction is spontaneous.
• ΔH: Change in Enthalpy (total heat content of the system).
• T: Absolute temperature in Kelvin (K).
• ΔS: Change in Entropy (disorder).

Interpreting ΔG:

• If ΔG < 0: The reaction is spontaneous. It releases free energy and can be harnessed to do work.
• If ΔG > 0: The reaction is non-spontaneous. It requires an input of free energy to proceed.
• If ΔG = 0: The system is at equilibrium. There is no net change in the concentrations of reactants and products.

2. Energy Changes in Reactions

2.1 Exothermic vs. Endothermic Reactions (Focus on Heat, ΔH)

This classification is based on the change in enthalpy (heat).

• Exothermic Reaction:

  • Definition: A reaction that releases energy in the form of heat. The products have lower enthalpy than the reactants.
  • Enthalpy Change: ΔH < 0 (negative).
  • Biological Example: Cellular respiration. The complete oxidation of glucose is highly exothermic, releasing energy that is partially captured as ATP and partially lost as body heat.

• Endothermic Reaction:

  • Definition: A reaction that absorbs energy in the form of heat from its surroundings. The products have higher enthalpy than the reactants.
  • Enthalpy Change: ΔH > 0 (positive).
  • Biological Example: Photosynthesis. Plants absorb light energy (a form of energy that drives the overall process) to convert CO₂ and water into energy-rich glucose. Melting of ice is a simpler physical example.

2.2 Exergonic vs. Endergonic Reactions (Focus on Free Energy, ΔG)

This classification is based on the change in Gibbs Free Energy and determines the spontaneity of a reaction.

• Exergonic Reaction:

  • Definition: A "spontaneous" reaction that proceeds with a net release of free energy.
  • Free Energy Change: ΔG < 0 (negative).
  • Metabolic Role: These are primarily catabolic reactions. They break down molecules and release energy that the cell can use.
  • Example: The hydrolysis of ATP.
    ATP + H₂O → ADP + Pᵢ (inorganic phosphate)
    This reaction has a ΔG of approximately -7.3 kcal/mol under standard conditions and is the primary source of energy for most cellular work.

• Endergonic Reaction:

  • Definition: A "non-spontaneous" reaction that absorbs free energy from its surroundings. It requires energy input to occur.
  • Free Energy Change: ΔG > 0 (positive).
  • Metabolic Role: These are primarily anabolic reactions. They build complex molecules and store energy.
  • Example: The synthesis of a protein from amino acids. Each peptide bond formation is an endergonic process.

2.3 Energy Coupling and ATP

Cells drive endergonic reactions by coupling them to highly exergonic reactions. The most common exergonic reaction used for coupling is the hydrolysis of ATP.

• ATP (Adenosine Triphosphate): Composed of adenine (a nitrogenous base), ribose (a sugar), and a chain of three phosphate groups. The bonds between the phosphate groups are high-energy because of the repulsive forces between the negatively charged phosphate ions.
• The ATP Cycle:
  1. Energy Release (Hydrolysis): When the terminal phosphate bond is broken by hydrolysis, ATP becomes ADP (Adenosine Diphosphate), and the energy released (ΔG < 0) is used to power cellular work (e.g., muscle contraction, active transport).
  2. Energy Storage (Phosphorylation): Energy from catabolism (like glucose breakdown) is used to add a phosphate group back to ADP, regenerating ATP. This is an endergonic process.

In this diagram, the exergonic hydrolysis of ATP provides the energy needed for an endergonic reaction to proceed.

3. Photosynthesis: Capturing Solar Energy

Photosynthesis is the anabolic process used by plants, algae, and some bacteria to convert light energy into chemical energy, storing it in the bonds of carbohydrates.

• Overall Equation: 6CO₂ + 6H₂O + Light Energy → C₆H₁₂O₆ + 6O₂
• Location: Chloroplasts

Photosynthesis occurs in two main stages:

3.1 Stage 1: Light-Dependent Reactions

• Objective: Convert light energy into chemical energy in the form of ATP and NADPH.
• Location: Thylakoid membranes within the chloroplast.
• Inputs:
  • Light
  • Water (H₂O)
  • ADP
  • NADP⁺
• Process:
  1. Photoexcitation: Pigments (like chlorophyll) in photosystems absorb photons of light, exciting electrons to a higher energy level.
  2. Photolysis: To replace the lost electrons, an enzyme splits water molecules, releasing electrons, protons (H⁺), and oxygen gas (O₂) as a byproduct.
  3. Electron Transport Chain (ETC): The high-energy electrons are passed along a series of protein complexes in the thylakoid membrane. As they move, their energy is used to pump H⁺ ions from the stroma into the thylakoid lumen, creating a proton gradient.
  4. Chemiosmosis & ATP Synthesis: The H⁺ ions flow back into the stroma down their concentration gradient through an enzyme called ATP synthase, which uses this flow to generate ATP from ADP and Pᵢ. This process is called photophosphorylation.
  5. NADPH Formation: After passing through a second photosystem, the re-energized electrons are transferred to NADP⁺, reducing it to NADPH, an electron carrier.
• Outputs:
  • ATP (provides energy for the Calvin Cycle)
  • NADPH (provides reducing power/electrons for the Calvin Cycle)
  • O₂ (released as a waste product)

3.2 Stage 2: Calvin Cycle (Light-Independent Reactions)

• Objective: Use the ATP and NADPH from the light reactions to convert CO₂ into sugar (G3P).
• Location: Stroma (the fluid-filled space) of the chloroplast.
• Inputs:
  • CO₂ (from the atmosphere)
  • ATP (from light reactions)
  • NADPH (from light reactions)
• Process (Simplified):
  1. Carbon Fixation: The enzyme RuBisCO attaches one CO₂ molecule to a five-carbon sugar called RuBP. This forms an unstable six-carbon compound that immediately splits into two three-carbon molecules.
  2. Reduction: Each three-carbon molecule is phosphorylated by ATP and then reduced by NADPH, converting it into Glyceraldehyde-3-phosphate (G3P), a three-carbon sugar.
  3. Regeneration: For every six G3P molecules produced, one exits the cycle to be used by the plant to make glucose and other organic compounds. The other five are recycled, using more ATP, to regenerate the three RuBP molecules needed for the cycle to continue.
• Outputs:
  • G3P (a 3-carbon sugar)
  • ADP and NADP⁺ (which return to the light-dependent reactions)

4. Cellular Respiration: Harvesting Chemical Energy

Cellular respiration is the primary catabolic pathway that breaks down glucose and other organic fuels to produce ATP.

• Overall Equation: C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + Energy (ATP + heat)

4.1 Stage 1: Glycolysis

• Objective: To split glucose into two molecules of pyruvate.
• Location: Cytosol.
• Oxygen Requirement: None (anaerobic).
• Process: A sequence of 10 enzyme-catalyzed reactions.
  • Phase 1: Energy Investment Phase: The cell spends 2 ATP molecules to phosphorylate the glucose molecule, making it less stable and ready for cleavage.
  • Phase 2: Energy Payoff Phase: The 6-carbon sugar is split into two 3-carbon molecules. These molecules are then oxidized, and their energy is harvested to produce 4 ATP and 2 NADH.
• Summary:
  • Inputs:
    • 1 Glucose (6C)
    • 2 ATP
    • 2 NAD⁺
  • Net Outputs:
    • 2 Pyruvate (3C molecules)
    • 2 ATP (4 produced - 2 invested)
    • 2 NADH (electron carriers)

4.2 Stage 2: Krebs Cycle (Citric Acid Cycle)

This stage completely oxidizes the products of glycolysis to CO₂. It occurs in two parts: Pyruvate Oxidation and the cycle itself.

• Location: Mitochondrial Matrix.
• Oxygen Requirement: Indirectly requires O₂ (aerobic). The NADH and FADH₂ produced must be re-oxidized by the electron transport chain, which requires oxygen as the final electron acceptor.

4.2.1 Preparatory Step: Pyruvate Oxidation

• Before the cycle begins, each pyruvate molecule from glycolysis is transported into the mitochondrion.
• Process:
  1. A carboxyl group is removed from pyruvate, releasing a molecule of CO₂.
  2. The remaining 2-carbon fragment is oxidized, and the electrons are transferred to NAD⁺, forming NADH.
  3. The 2-carbon fragment (an acetyl group) attaches to Coenzyme A, forming Acetyl-CoA.
• Outputs (per pyruvate): 1 Acetyl-CoA, 1 NADH, 1 CO₂.
  (Note: This happens twice per glucose molecule).

4.2.2 The Citric Acid Cycle

• Objective: To complete the breakdown of glucose by oxidizing Acetyl-CoA and harvesting high-energy electrons in the form of NADH and FADH₂.
• Process:
  1. Acetyl-CoA (2C) joins with a 4-carbon molecule, oxaloacetate, to form a 6-carbon molecule, citrate.
  2. The citrate molecule then goes through a series of eight steps where it is oxidized.
  3. In the process, two carbon atoms are released as CO₂.
  4. Energy is captured in the form of 3 NADH, 1 FADH₂, and 1 ATP (or GTP, which is equivalent) per turn of the cycle.
  5. The cycle regenerates the starting 4-carbon oxaloacetate molecule, ready to accept another Acetyl-CoA.
• Summary (per turn of the cycle, i.e., per Acetyl-CoA):
  • Inputs:
    • 1 Acetyl-CoA
    • 3 NAD⁺
    • 1 FAD
    • 1 ADP + Pᵢ
  • Outputs:
    • 2 CO₂
    • 3 NADH
    • 1 FADH₂
    • 1 ATP

Total Yield from Krebs Cycle (per initial Glucose molecule):
Since one glucose produces two pyruvate molecules, the Krebs cycle and its prep step run twice.

• Pyruvate Oxidation (x2): 2 NADH, 2 CO₂
• Krebs Cycle (x2): 6 NADH, 2 FADH₂, 2 ATP, 4 CO₂
• Total: 8 NADH, 2 FADH₂, 2 ATP, 6 CO₂

The high-energy electron carriers (NADH and FADH₂) produced during glycolysis and the Krebs cycle will proceed to the final stage of cellular respiration, the Electron Transport Chain, where the majority of ATP is produced.