Cellular Energetics

Thermodynamics and Free Energy

The first law of thermodynamics states that energy cannot be created or destroyed, only transformed. The second law tells us that every energy transfer increases the entropy of the universe. In biology, we track these changes with Gibbs free energy (G).

A negative change in free energy (delta G < 0) indicates an exergonic reaction that releases usable energy. A positive delta G marks an endergonic reaction that requires energy input. Cells couple exergonic reactions (like ATP hydrolysis) to endergonic ones (like amino acid polymerization) so that thermodynamically unfavorable processes can proceed.

Enthalpy (H) represents total heat content, while entropy (S) measures molecular disorder. The Gibbs equation delta G = delta H - T(delta S) ties them together and predicts spontaneity at a given temperature.

ATP Structure and Hydrolysis

ATP consists of adenine, ribose, and three phosphate groups linked by phosphoanhydride bonds. Hydrolysis of the terminal phosphate yields ADP + Pi and releases energy because the products are more stable than the reactant. Cells regenerate ATP from ADP through substrate-level phosphorylation and oxidative phosphorylation.

The cell maintains a high ATP-to-ADP ratio far from equilibrium, which maximizes the energy available from each hydrolysis event. A resting human turns over roughly their own body weight in ATP every day, illustrating how rapidly this molecule cycles between synthesis and consumption.

Enzyme Catalysis and Activation Energy

Enzymes are biological catalysts - usually proteins - that accelerate reactions by lowering the activation energy (Ea) without changing the overall delta G of the reaction. They achieve this through an induced-fit model in which the active site reshapes slightly upon substrate binding, stabilizing the transition state.

Enzyme activity depends on temperature, pH, substrate concentration, and the presence of inhibitors or activators. Competitive inhibitors bind the active site, while noncompetitive (allosteric) inhibitors bind elsewhere and change enzyme conformation. Feedback inhibition, where a downstream product inhibits an upstream enzyme, is a common regulatory strategy in metabolic pathways.

Photosynthesis

Photosynthesis occurs in the chloroplast and proceeds in two stages. The light-dependent reactions take place in the thylakoid membranes, where photosystems I and II capture photons, split water (photolysis), and generate ATP and NADPH via the electron transport chain and chemiosmosis. Oxygen is released as a byproduct.

The Calvin cycle (light-independent reactions) operates in the stroma. The enzyme RuBisCO fixes CO2 onto ribulose bisphosphate (RuBP) to produce 3-phosphoglycerate (3-PGA), which is then reduced to glyceraldehyde-3-phosphate (G3P) using the ATP and NADPH from the light reactions. Three turns of the cycle fix three CO2 molecules and yield one net G3P, which can be used to build glucose and other organic molecules.

Cellular Respiration

Cellular respiration is the aerobic oxidation of glucose to CO2 and H2O, with energy captured as ATP. It proceeds through four stages: glycolysis (cytoplasm), pyruvate oxidation (mitochondrial matrix), the citric acid cycle (matrix), and oxidative phosphorylation via the electron transport chain (inner mitochondrial membrane).

Glycolysis splits one glucose (6C) into two pyruvate (3C), yielding a net 2 ATP and 2 NADH. Pyruvate is then decarboxylated to acetyl-CoA, producing CO2 and NADH. Each acetyl-CoA enters the citric acid cycle, generating 3 NADH, 1 FADH2, 1 GTP (equivalent to ATP), and 2 CO2 per turn.

The electron transport chain accepts electrons from NADH and FADH2, passing them through complexes I-IV to molecular oxygen. The energy released pumps H+ ions into the intermembrane space, and ATP synthase harnesses this proton-motive force to produce approximately 30-32 ATP per glucose via chemiosmosis.

Fermentation

When oxygen is unavailable, cells regenerate NAD+ through fermentation so glycolysis can continue. Lactic acid fermentation reduces pyruvate directly to lactate (in muscle cells and some bacteria). Alcohol fermentation decarboxylates pyruvate to acetaldehyde, then reduces it to ethanol (in yeast). Both pathways yield only 2 ATP per glucose - far less than aerobic respiration.

Photosynthesis vs. Cellular Respiration

These two processes are complementary: the products of one are the reactants of the other.