Bioenergetics and Metabolic Energy Transfer in Human Physiology

Bioenergetics

The study of energy changes accompanying biochemical reactions. It explains how energy is produced, transferred, and used in living systems.

Energy Imbalance in Humans

Malnutrition results from an imbalance between energy intake and expenditure. Undernutrition (low energy intake) causes protein-energy malnutrition (PEM), while overnutrition (excess intake) leads to fat storage and obesity. Prolonged starvation causes death when energy reserves are exhausted.

Gibbs Free Energy (ΔG)

Measures the amount of energy available to do work in a system. Reactions with negative ΔG (exergonic) release energy and occur spontaneously; reactions with positive ΔG (endergonic) require energy input.

Exergonic vs Endergonic Reactions

Exergonic: spontaneous, energy-releasing (−ΔG). Endergonic: nonspontaneous, energy-requiring (+ΔG). These reactions often occur together (coupled reactions) to maintain energy balance.

Exergonic vs Exothermic Difference

Exergonic reactions involve free energy (ΔG), whereas exothermic reactions involve heat release. Biological systems depend on free energy, not just heat energy.

Coupled Reactions

Reactions linked so that energy released by one (exergonic) drives another that requires energy (endergonic). Example: A → B (releases energy) powers C → D (requires energy). Some energy is always lost as heat.

Metabolism Overview

The total chemical activity within a living organism that maintains life. Includes both catabolism (breakdown reactions releasing energy) and anabolism (building reactions consuming energy).

Catabolism vs Anabolism

Catabolism breaks down complex molecules, releasing free energy. Anabolism builds complex molecules, using free energy. Energy is temporarily stored in high-energy intermediates like ATP or creatine phosphate since these pathways occur separately in time and space.

High-Energy Intermediates — Overview

Molecules that temporarily store and transfer energy between metabolic reactions. Main examples include ATP (adenosine triphosphate) and creatine phosphate (phosphocreatine).

ATP — Structure & Function

Adenosine triphosphate contains two high-energy phosphate bonds. It's a nucleotide produced during catabolic reactions and acts as the universal energy currency. Only small amounts are stored in cells.

Creatine Phosphate (Phosphocreatine)

Found in skeletal muscle and brain. Acts as a rapid energy reserve that regenerates ATP during brief, intense activity by donating a phosphate group to ADP.

Sources of Free Energy

Major catabolic pathways that generate ATP: glycolysis, citric acid cycle, oxidative phosphorylation (respiratory chain), and phosphagenesis (creatine phosphate system).

Uses of Free Energy

Anabolic pathways consume ATP to build complex molecules: gluconeogenesis, glycogenesis, lipogenesis, protein synthesis, and nucleic acid synthesis (DNA, RNA).

ATP-Driven Reactions

ATP allows endergonic (energy-requiring) reactions to proceed by coupling with its own hydrolysis. Example: 1️⃣ Glucose + Pi → Glucose-6-phosphate (ΔG = +13.8 kJ/mol, endergonic) 2️⃣ ATP → ADP + Pi (ΔG = −30.5 kJ/mol, exergonic)

Coupled Glucose Phosphorylation

When reactions are combined: Glucose + ATP → Glucose-6-phosphate + ADP. Net ΔG = −16.7 kJ/mol (exergonic). The reaction proceeds spontaneously and irreversibly due to the large negative ΔG.

Biological Oxidations — Overview (Ch. 12)

Energy in humans depends on oxidation reactions that transfer electrons or hydrogen.

Oxidation

Gain of O₂ / loss of H or electrons.

Reduction

Gain of H or electrons / loss of O₂.

Oxidoreductases

Enzyme class catalyzing oxidation-reduction reactions. Includes oxidases, dehydrogenases, hydroperoxidases, and oxygenases.

Oxidases

Remove hydrogen from a substrate and use O₂ as the hydrogen acceptor to form H₂O or H₂O₂. Reaction: AH₂ + O₂ → A + H₂O₂.

Cofactors of Oxidases

Fe or Cu.

Coenzymes of Oxidases

FAD or FMN (flavoproteins derived from riboflavin, vitamin B₂).

Dehydrogenases

Transfer hydrogen between substrates (not involving O₂). Use coenzymes NAD⁺ or NADP⁺ derived from niacin (vitamin B₃). Produce reduced forms NADH or NADPH for use in the respiratory chain and biosynthesis.

Hydroperoxidases

Enzymes that break down peroxides.

Catalase

2H₂O₂ → 2H₂O + O₂.

Peroxidases

Use reduced glutathione to detoxify peroxides (H₂O₂ + AH₂ → 2H₂O + A).

Oxygenases

Incorporate one or both atoms of O₂ into substrates. Includes monooxygenases (mixed-function oxidases).

Cytochrome P450 enzymes

Metabolize drugs and steroids via hydroxylation.

Superoxide dismutase

Protects against O₂⁻ free radicals.

Respiratory Chain (Electron Transport Chain, ETC)

Reduced coenzymes NADH and FADH₂ donate electrons and hydrogen to the respiratory chain in the mitochondrial inner membrane. Electrons pass through complexes I-IV to O₂, forming H₂O.

Mitochondrial Structure

Outer membrane — semipermeable with porins; Inner membrane — selective, houses ETC complexes, ATP synthase, and cardiolipin; Intermembrane space — H⁺ accumulation area; Matrix — contains mitochondrial DNA and enzymes for the citric acid cycle.

Chemiosmotic Theory (Oxidative Phosphorylation)

Electron flow through complexes I, III, and IV pumps H⁺ from the matrix to the intermembrane space, generating an electrochemical (proton) gradient.

ATP Synthase (F₀-F₁ Complex)

H⁺ reenters the matrix through ATP synthase. Flow through the F₀ subunit drives ATP formation in the F₁ subunit: ADP + Pi → ATP.

ATP Yield per Reduced Coenzyme

1 NADH (mitochondrial) → 2.5 ATP; 1 FADH₂ (mitochondrial) → 1.5 ATP; 1 cytosolic NADH → 2.5 or 1.5 ATP (depends on shuttle system used).

Glycerophosphate Shuttle (Most Tissues)

Transfers cytosolic NADH electrons to the ETC via FAD.

Malate-Aspartate Shuttle (Heart)

More efficient shuttle used in cardiac tissue.

Respiratory Chain Regulation

Controlled by availability of ADP, NADH/FADH₂, and O₂.

Overall Energy Control in Cells

The respiratory chain's regulation keeps biological energy conversion efficient, avoiding excessive heat loss while maintaining sufficient ATP for metabolic needs.