Chapter 3: Bioenergetics, Enzymes & Metabolism

The First Law confirms energy is conserved and transduced between different forms, such as chemical, electrical, or mechanical energy. The Second Law mandates that events proceed spontaneously in a direction that increases the entropy (disorder) of the universe, moving systems toward lower free energy (Delta G). Reactions are classified as exergonic (spontaneous, negative Delta G) or endergonic (non-spontaneous, positive Delta G). Cells function in a steady state, far from equilibrium, continuously utilizing the universal energy currency, ATP, which is a high-energy molecule due to its large negative standard free-energy change upon hydrolysis. Endergonic reactions, such as the synthesis of glutamine, are driven forward by coupling them to the highly favorable hydrolysis of ATP via common intermediates. To overcome the inherent barrier of activation energy (EA) required for chemical transformations, cells rely on enzymes, which are specialized protein catalysts that dramatically increase reaction rates by lowering the EA without affecting the reaction's equilibrium position. Enzymes accomplish this by binding substrates at their active sites, stabilizing the transition state through mechanisms like inducing strain, ensuring proper substrate orientation (reducing entropy), and altering substrate reactivity. Enzyme kinetics are quantified by the Michaelis-Menten model, which defines the maximal velocity (Vmax) and the Michaelis constant (KM), a measure often linked to substrate affinity. Enzyme activity is regulated by both reversible (competitive or noncompetitive) and irreversible inhibitors, a principle leveraged in antibiotic design, although pathogens rapidly evolve antibiotic resistance through mechanisms like enzymatic destruction (e.g., beta-lactamase) or target modification. Metabolism is organized into catabolic (convergent, energy-releasing, producing ATP and NADH) and anabolic (divergent, energy-consuming, requiring reducing power from NADPH) pathways. Glucose catabolism initiates with glycolysis in the cytosol, generating a net gain of ATP through substrate-level phosphorylation. Under anaerobic conditions, fermentation regenerates NAD+ by converting pyruvate to compounds like lactate or ethanol, ensuring glycolysis continues. Metabolic flow is finely controlled by modifying key regulatory enzymes, utilizing covalent modification (like phosphorylation) and allosteric modulation such as feedback inhibition, where a pathway's end product inhibits its first committed enzyme. Plants demonstrate sophisticated metabolic control using a circadian oscillator to anticipate light availability for photosynthesis, while medical imaging exploits the Warburg effect (high tumor glycolysis) using tracers like 18F-FDG in PET scans to localize metabolically active tissue.