Cellular Respiration & Glycolysis

Cellular Energy Efficiency and Thermodynamics

• Complete aerobic oxidation of one mole of glucose releases a gross energy output of ext{~686 kcal (2.87 MJ)}.
  • Scientists determine this value by burning glucose in a calorimeter and measuring the heat released.
• Living cells do not convert all of this energy directly to ATP; instead they capture roughly 234 \text{ kcal/mol} (≈34 % of the total) in the two terminal (phosphoanhydride) bonds of ATP.
  • Remaining energy is dissipated mainly as heat, which can still perform useful work (e.g., maintaining body temperature in endotherms).
• Cellular efficiency (≈34 %) is comparable to internal-combustion engines (≈25–50 %).
  • Key metabolic design principle: oxidation of glucose proceeds through many small, enzyme-controlled steps, each of which releases modest energy increments that can be
    coupled directly to endergonic processes such as
    • reduction of \mathrm{NAD^{+}} to \mathrm{NADH}
    • phosphorylation of \mathrm{ADP} to \mathrm{ATP}.

Pathway Choices After Glycolysis

• When \mathrm{O_2} is present (aerobic conditions):
  1. Pyruvate Oxidation → 2 molecules pyruvate (3 C) are converted to 2 molecules acetyl-CoA (2 C) + 2 \mathrm{CO_2}.
  2. Citric Acid Cycle → each acetyl group is completely oxidised to \mathrm{CO2}, generating additional \mathrm{NADH}, \mathrm{FADH2} and \mathrm{ATP / GTP}.
• When \mathrm{O_2} is absent (anaerobic conditions): • Fermentation diverts pyruvate to regenerate \mathrm{NAD^{+}} so glycolysis can continue.
  • In plants & fungi: pyruvate → \mathrm{CO_2} + ethanol (2-C).
  • In animals & many bacteria: pyruvate → lactate (3-C).
    • Net energy obtained under fermentation ≈ 28 \text{ kcal/mol} glucose (≈2 % efficiency).

Glycolysis: Core Facts

• Location : cytosol (cytoplasm) of all living cells.
• Length : 10 enzyme-catalysed steps, universally conserved.
• Net outputs per glucose:
  • 2 pyruvate
  • 2 ATP (net; 4 produced – 2 consumed)
  • 2 \mathrm{NADH}
• Two functional phases
  1. Energy-Investment Stage (Steps 1–5)
  • Two ATP are hydrolysed; their phosphate groups are attached to glucose derivatives.
    • 1st phosphorylation at C-6 \rightarrow glucose-6-phosphate.
    • Isomerisation \rightarrow fructose-6-phosphate.
    • 2nd phosphorylation at C-1 \rightarrow fructose-1,6-bisphosphate.
  • Both phosphorylation reactions are endergonic condensations driven by ATP → ADP + \mathrm{P_i}.
  • Fructose-1,6-bisphosphate is cleaved (aldolase) to two triose phosphates:
    • dihydroxyacetone phosphate (DHAP)
    • glyceraldehyde-3-phosphate (G3P); DHAP is rapidly isomerised to a second G3P — yielding 2 × G3P.
  1. Energy-Harvesting Stage (Steps 6–10)
  • Each G3P is oxidised and phosphorylated by inorganic phosphate (Pi), generating 2 × \mathrm{NADH}.
  • Substrate-level phosphorylation twice per triose produces 4 × ATP in total.
  • End product per glucose : 2 × pyruvate.

Comparative Energy Yields

• Aerobic Pathway (glycolysis + pyruvate oxidation + citric acid cycle + oxidative phosphorylation):
  • Up to ~32 ATP per glucose in eukaryotes (exact number varies with shuttle systems & proton-pumping stoichiometry).
• Fermentation Pathway (glycolysis only):
  • 2 ATP per glucose.

Conceptual / Real-World Connections

• Stepwise energy release avoids catastrophic heat loss and maximises capture efficiency — an evolutionary solution mirrored in industrial power plants that use multi-stage turbines.
• Regeneration of \mathrm{NAD^{+}} is the critical control point under anaerobic conditions; failure to re-oxidise NADH would halt glycolysis within seconds.
• Fermentation end-products have ecological & economic relevance:
  • Ethanol in brewing, biofuels.
  • Lactate as an indicator of oxygen debt in muscle physiology.

Ethical & Practical Implications

• Understanding cellular energy efficiency guides biomedical strategies for metabolic disorders (e.g., targeting anaerobic glycolysis in cancer cells — the “Warburg effect”).
• Biotechnological optimisation of fermentation pathways underpins sustainable bio-manufacturing and reduces dependence on fossil fuels.

Key Numerical and Equation References

• Overall aerobic equation : \mathrm{C6H{12}O6 + 6\ O2 \;\rightarrow\; 6\ CO2 + 6\ H2O +\; \text{energy}}.
• Aerobic energy capture : 234 \text{ kcal captured} / 686 \text{ kcal released} = 0.34 \; (34 \%).
• Anaerobic energy yield : 28 \text{ kcal} / 686 \text{ kcal} \approx 0.02 \; (2 \%).