BIOSCI 101 Lecture 3

Historical Context & Introductory Anecdotes

• Opening quotation (Ludwig Boltzmann): “The struggle for existence of living beings is not for the fundamental constituents of food but for the position of free energy obtained chiefly by the means of the green plant from the transfer of radiant energy from the hot sun to the cold earth.”
  • Sets thermodynamic framing of life.

• Lecturer’s tradition of inserting student-pet photos and heart MRI to humanise topic.

Fundamental Concepts of Bioenergetics

• Energy is stored in chemical bonds—especially in reduced bonds (gain of electrons).
  • Mnemonic reminder: LEO says GER (Loss of Electrons = Oxidation; Gain of Electrons = Reduction).

• Cellular goal: extract bond energy → transfer to ATP (adenosine triphosphate) for immediate use.

• Core aims of lecture:
  • Explain why ATP is the universal, ancient, short-term energy store.
  • Relate ATP energetics to the laws of thermodynamics and to $\Delta G$ (Gibbs free energy).
  • Show how hydrolysis of ATP (primarily first phosphate) drives biological work.

Energy Flow in Ecosystems

• Source hierarchy: Sun → photo-autotrophs (plants, algae, photosynthetic bacteria) → herbivores → carnivores.

• At each trophic transfer energy is lost as heat; ultimately all solar energy returns to space as infrared radiation.

• Ecosystem schematic:
  • Photosynthesis: $\text{CO}<em>2 + \text{H}</em>2\text{O} \xrightarrow{light} \text{Carbohydrates}$ (organic molecules).
  • Catabolism (oxidative respiration): Organic molecules + $\text{O}<em>2$ → $\text{CO}</em>2 + \text{H}_2\text{O} + \text{ATP} + \text{Heat}$.

• Anabolism vs Catabolism:
  • Anabolic pathways build macromolecules (e.g.
  proteins, DNA).
  • Catabolic pathways break nutrients down to capture energy (focus of upcoming lectures).

Human Metabolism & Energy Stores

• Digestive work itself consumes ATP (chewing, peristalsis, acid secretion via proton pumps).

• Indigestible cellulose → faeces; excess nitrogen from amino acids → urea in urine.

• Intracellular fate of absorbed nutrients:
  • Biosynthesis (anabolism) or
  • Cellular respiration in mitochondria → ATP.

• Major body stores (fasted adult):
  • Muscle glycogen ≈ 150 g.
  • Liver glycogen ≈ 80 g.
  • Adipose triglyceride ≈ 15 kg (largest energy reservoir).
  • Structural protein large but guarded; catabolised only in starvation.

• Organ cross-talk: Liver releases glucose; adipose tissue releases free fatty acids; skeletal muscle largely imports, not exports, fuels (except amino acids during starvation).

Caloric Content & Bomb Calorimetry

• Device by Antoine Lavoisier (1790s): sample + ignition in sealed vessel immersed in measured water volume; temperature rise → energy content.

• Average heats of combustion:
  • Carbohydrate: $\approx 4\;\text{kcal g}^{-1}$ (≈17 kJ g⁻¹).
  • Protein: $\approx 4\;\text{kcal g}^{-1}$ (similar to carbs but biologically lower after de-amination).
  • Alcohol: $\approx 7\;\text{kcal g}^{-1}$ but metabolically costly/toxic.
  • Fat: $\approx 9\;\text{kcal g}^{-1}$ (≈38 kJ g⁻¹).

• In vivo, glucose yields more ATP per O₂ than fat; alcohol yields less usable energy due to detox cost.

ATP: Structure, Properties, and Cycle

• Components: adenine base (nitrogenous base) + ribose (RNA sugar, hence older than DNA) + three phosphates.

• Physiological form: phosphates are ionised (negatively charged).

• Typical cellular concentration:
  • Heart muscle ≈ 8–10 mM ATP vs ≈ 0.05 mM ADP (∼200 : 1 ratio).

• ATP Cycle:

  1. Hydrolysis: $\text{ATP} + \text{H}<em>2\text{O} \rightarrow \text{ADP} + \text{P}</em>i + \text{Energy}$ (exergonic).

  2. Energy drives endergonic work (ion pumps, motors, biosynthesis).

  3. Phosphorylation: ADP + $\text{P}_i$ + energy from catabolism → ATP (regeneration).

• Work examples:
  • Ion transporters (e.g.
  Na⁺/K⁺ pump, Ca²⁺ pump).
  • Kinesin walking vesicles along microtubules.
  • Myosin sliding actin in muscle contraction.
  • Vesicle trafficking & neurotransmitter loading.

Why ATP? Evolutionary & Chemical Rationale

• All life uses ATP; alternates (CTP, GTP, UTP, creatine-P, poly-P) exist but at lower concentrations.

• ATP slightly more water-stable and chemically manageable than other NTPs; enough energy yet not prone to uncontrolled hydrolysis.

• Pre-biotic synthesis hypothesis (Lane & Martin, 2022):
  • Ancient pathway uses acetyl phosphate + Fe²⁺ to phosphorylate ADP → ATP without needing pre-existing ATP (overcomes “ATP needs ATP” paradox).
  • ADP uniquely binds Fe²⁺/acetyl-P complex better than other nucleotides, explaining evolutionary selection.

• Bacterial polyphosphates: long inorganic phosphate chains can store energy and chelate free iron during septicemia, but less efficient than ATP.

Mechanisms of ATP-Driven Work

• Electrostatic repulsion model:
  • Adjacent negative charges on triphosphate repel; breaking terminal bond releases electrostatic tension.
  • Mg²⁺/Ca²⁺ often coordinate between phosphates, orienting molecule for enzyme recognition and possibly accelerating terminal phosphate ejection.

• Energy distribution:
  • ATP → ADP + $\text{P}_i$ releases $\approx −30.5\;\text{kJ mol}^{-1}$.
  • ATP → AMP + PPi releases $\approx −32.2\;\text{kJ mol}^{-1}$; therefore only ≈2 kJ extra from second bond → vast majority of usable energy in first phosphate.

• Mass-action leverage: huge ATP : ADP ratio keeps reactions far from equilibrium, providing a “water tower” of free energy.

Thermodynamics & Gibbs Free Energy

• First Law (Energy conservation): $\Delta H = q + w$ (heat + work).

• Second Law (Entropy): Universe’s disorder (entropy, $S$) always increases; living systems locally decrease entropy by creating greater entropy in surroundings.

• Gibbs equation: $\Delta G = \Delta H - T\Delta S$
  • $\Delta G < 0$ → spontaneous/exergonic → can perform work. • $\Delta G = 0$ → equilibrium. • $\Delta G > 0$ → non-spontaneous/endergonic (requires energy).

• Magnitude of $|\Delta G|$ indicates maximum theoretical work, not reaction rate (kinetics depend on enzymes, diffusion, temperature).

Gibbs Free Energy in Biological Reactions

• Analogies:
  • Compressed gas separated by partition → release increases entropy, performs work.
  • Hydro-dam: elevated water (potential energy) → turbines (work) → equilibrium in lower basin.

• Life as anti-entropy machine: maintains ordered state (low intracellular entropy) by exporting heat and waste (raising environmental entropy).

• Diffusion or ion pumping across membranes: concentrating ions decreases entropy; releasing gradient allows work (e.g.
  ATP synthase uses proton gradient).

Concentration Effects & Mass Action

• Reaction direction influenced by reactant/product ratios:
  • High [ATP] & low [ADP] push ATP-dependent reactions forward.
  • Product accumulation can produce feedback inhibition or drive reverse reaction if concentrations change.

Case Study: Glutamine Synthetase (Coupled Reaction)

• Need to convert neuronal glutamate (excitatory neurotransmitter) → glutamine to avoid excitotoxicity.

• Uncoupled reaction: $\text{Glutamate} + \text{NH}_3 \rightarrow \text{Glutamine}$ has $\Delta G = +3.4\;\text{kJ mol}^{-1}$ (unfavourable).

• Enzymatic strategy:

  1. Phosphorylate glutamate using ATP → γ-glutamyl-phosphate (adds energy).

  2. Nucleophilic attack by $\text{NH}<em>3$ → glutamine + $\text{P}</em>i$.

1. Overall: $\Delta G_{\text{net}} = +3.4 - 17.6 = -14.2\;\text{kJ mol}^{-1}$ (favourable).

• Demonstrates ATP’s ability to drive otherwise impossible chemistry.

Key Numerical & Formula Summary

• ATP hydrolysis (physiological conditions): $\approx -30.5\;\text{kJ mol}^{-1}$.

• ATP concentration (cardiac myocyte): 8–10 mM; ADP ≈0.05 mM.

• Macronutrient energy densities:
  • Carbs & Protein ≈17 kJ g⁻¹, Alcohol ≈29 kJ g⁻¹, Fat ≈38 kJ g⁻¹.

• Gibbs free energy: $\Delta G = \Delta H - T\Delta S$.

• Enthalpy: $\Delta H = q + w$.

Ethical, Philosophical & Practical Implications

• Understanding ATP energetics underlies medical interventions (e.g.
  cardiac ischemia, metabolic disorders).

• Polyphosphate-iron chelation insight may inform sepsis treatments.

• Recognising energy cost of biosynthesis emphasises nutritional requirements during illness or growth.

• Thermodynamic framing reinforces sustainability: biological systems unavoidably generate heat/entropy; efficient energy use and trophic inefficiencies inform food-chain management.