Thermodynamics & Metabolic Basics

Thermodynamics in Biological Reactions

• Terminology refresh
  • Chemistry often uses “endothermic / exothermic” (heat in / heat out) and “ectothermic / ecto-” but these ignore changes in usable energy (Gibbs free energy).
  • Biology prefers “endergonic / exergonic” because they reference \Delta G (usable energy in the system).
  • \Delta G < 0 ⇒ exergonic (energy released to surroundings)
  • \Delta G > 0 ⇒ endergonic (energy absorbed from surroundings)
  • \Delta G = 0 ⇒ equilibrium, no net progress
• Definition of Gibbs free energy
  • \Delta G = \Delta H - T\Delta S
  • \Delta H : change in enthalpy (total bond energy / heat content)
  • \Delta S : change in entropy (disorder)
  • T : absolute temperature in Kelvin
• Importance for biologists
  • T\Delta S term shows why temperature profoundly influences reaction rates.
  • At higher T there are more molecular collisions, so reactions run faster even without enzymes.

Entropy, Enthalpy & the Cell

• Entropy = disorder; living cells constantly fight internal increases in entropy by doing work.
• While a cell lowers its own internal entropy, it invariably raises entropy of the universe by releasing heat—life is not a closed system.

Temperature & Concentration Effects

• Raising ambient temperature → linear rise in collision frequency → faster uncatalyzed reactions.
• Raising solute concentration has the same collision-boosting effect.

Familiar Examples of Energy Change

• Exergonic
  • Lighting a campfire: wood (high potential energy) → heat + light + ash (low potential energy).
  • Caramelising / burning sugar in the kitchen.
• Endergonic
  • Block of ice melting or subliming at room temperature: absorbs heat from air.

Coupling Endergonic & Exergonic Reactions

• Cells rarely allow a stand-alone endergonic step; they couple it to an exergonic step.
  • Analogy: two interlocked gears; the exergonic gear releases energy that turns the endergonic gear.
• Core cellular coupling mechanisms
  1. Electron transfer (redox chemistry)
  2. Phosphate-group transfer (phosphorylation)

Redox Chemistry (Oxidation–Reduction)

• Language pitfalls
  • Oxidation ≠ “adding O”; it means loss of electrons.
  • Reduction (counter-intuitively) = gain of electrons.
  • Mnemonics: “OIL RIG” or “LEO the lion says GER”
  • OIL / LEO – Oxidation Is Loss / Lose Electrons = Oxidation
  • RIG / GER – Reduction Is Gain / Gain Electrons = Reduction
• Energetic relation
  • Oxidation steps are usually exergonic (release energy).
  • Reduction steps are usually endergonic (require energy input).
• Electrons often move with a proton (H⁺). Thus reduction often means adding an H, oxidation often means removing an H.

Cellular Respiration as a Master Redox Example

• Global equation
  • C6H{12}O6 + 6O2 \;\xrightarrow{\text{enzymes}}\; 6CO2 + 6H2O + \text{energy}
• Interpretations
  • Glucose is oxidised to CO_2 (loses electrons).
  • Oxygen is reduced to H_2O (gains electrons).
  • Released energy captured as ATP & electron carriers.
  • Your exhaled CO_2 = carbon atoms from food; water formed is excreted in urine/sweat.

Electron Carriers – Molecular “Rechargeable Batteries”

• NAD⁺ / NADH (nicotinamide adenine dinucleotide)
  • Oxidised form: NAD^+
  • Reduced form: NADH + H^+ (accepted 2 e⁻ + 1 H⁺)
• FAD / FADH₂ (flavin adenine dinucleotide)
  • Oxidised: FAD
  • Reduced: FADH_2
• Charging sequence (generic)
  • Exergonic reaction releases 2 e⁻ + 2 H⁺
  • NAD^+ + 2e^- + H^+ \rightarrow NADH (one H⁺ remains free)
• Reduced carriers later donate e⁻ to other pathways (electron transport chain, etc.).

ATP – The Energy Currency

• Structure: adenine + ribose + three phosphates (triphosphate tail = coiled spring).
• Hydrolysis
  • ATP + H2O \rightarrow ADP + Pi + 7.3\;\text{kcal mol}^{-1} (standard conditions)
• Why so energetic?
  • Three adjacent negative charges repel; breaking the bond relieves electrostatic tension.
• Cells constantly cycle ATP ⇌ ADP + P_i; food energy “deposits” ATP, cellular work “spends” it.
• Phosphorylation of a target molecule (adding P_i) generally “turns it on” by raising its free energy.

Enzymes – Biological Catalysts

• Proteins that lower activation energy (E_a) without affecting \Delta G.
• Concepts
  • Substrate = reactant(s) that bind the enzyme.
  • Active site = pocket that specifically fits the substrate; often undergoes induced fit (enzyme hugs substrate).
  • Transition state = strained-bond state; enzymes stabilise it → easier bond-breaking/forming.
  • Enzymes emerge unchanged → reusable.

Visualization of Catalysis

• Without enzyme: large E_a hill.
• With enzyme: hill is lower → reaction rate skyrockets.

Saturation Kinetics

• Rate vs substrate concentration graph
  • Initial linear region (substrate scarce).
  • Plateau (Vmax) when all active sites are occupied (enzyme saturated).
• To speed further, cell must synthesize more enzyme molecules.

Environmental & Genetic Effects on Enzymes

• Temperature, pH, ionic strength can alter 3-D shape ⇒ alter activity.
• Mutations change primary structure ⇒ can enhance, cripple, or abolish catalytic efficiency.

Regulation of Enzyme Activity

• Competitive inhibition
  • Regulatory molecule resembles substrate & binds active site → blocks substrate.
• Allosteric regulation
  • Regulatory molecule binds elsewhere.
  • Allosteric activation: stabilises active conformation.
  • Allosteric inhibition: stabilises inactive conformation.
• Covalent modification
  • Reversible: phosphorylation/de-phosphorylation toggles activity.
  • Irreversible: peptide bond cleavage (proteolytic activation or permanent inactivation).

Metabolic Pathways & Feedback Control

• Metabolism = thousands of enzyme-mediated steps converting nutrients → energy + biomolecules.
• Pathways resemble domino chains: Product of one enzyme = substrate for next.
• Feedback inhibition
  • Final product accumulates → binds allosteric site of first committed enzyme → shuts the pathway.
  • Prevents wasteful over-production and conserves precursors & ATP.

Practical / Ethical / Real-World Connections

• Understanding \Delta G and coupling is essential for bioengineering (e.g., designing synthetic metabolic pathways).
• Enzyme inhibitors are foundational in pharmacology (antibiotics, anticancer drugs, statins).
• Temperature-linked reaction rates explain fever benefits & heat-stroke dangers.
• Feedback loops illustrate homeostasis principles—cells, organs, ecosystems regulate themselves similarly.