Chapter 23

CHAPTER 23: BIOCHEMICAL ENERGY PRODUCTION

Overview of Metabolism

Metabolism encompasses all the biochemical reactions that occur in living organisms, including both the breakdown of molecules to produce energy and the synthesis of new cellular components.

• Catabolism: The breakdown of complex molecules into simpler ones, releasing energy.

• Anabolism: The synthesis of complex molecules from simpler ones, requiring energy input.

• Metabolic Pathways: Series of enzyme-catalyzed reactions where the product of one reaction serves as the substrate for the next.

• Example: The citric acid cycle (Krebs cycle) is a central catabolic pathway in aerobic organisms.

Mitochondria and Cellular Respiration

Mitochondria are the primary sites of ATP production in eukaryotic cells, hosting the citric acid cycle and the electron transport chain (ETC).

• Structure: Double-membraned organelle with an inner membrane (site of ETC) and a matrix (site of citric acid cycle).

• Function: Oxidize nutrients to generate ATP via oxidative phosphorylation.

• Example: The inner mitochondrial membrane is less permeable than the outer membrane, maintaining the proton gradient necessary for ATP synthesis.

CITRIC ACID CYCLE (KREBS CYCLE)

Overview and Steps

The citric acid cycle is a series of enzyme-catalyzed reactions that oxidize acetyl-CoA to CO2 and generate high-energy electron carriers (NADH, FADH2).

• Main Steps:

  1. Acetyl-CoA combines with oxaloacetate to form citrate (C6).

  2. Citrate is isomerized to isocitrate.

  3. Isocitrate is oxidized and decarboxylated to α-ketoglutarate (C5), producing CO2 and NADH.

  4. α-Ketoglutarate is further oxidized and decarboxylated to succinyl-CoA (C4), producing CO2 and NADH.

  5. Succinyl-CoA is converted to succinate, generating GTP (or ATP).

  6. Succinate is oxidized to fumarate, producing FADH2.

  7. Fumarate is hydrated to malate.

  8. Malate is oxidized to oxaloacetate, producing NADH.

• Products per turn: 3 NADH, 1 FADH2, 1 GTP (or ATP), 2 CO2

• Example: Two turns of the cycle are required per glucose molecule (since each glucose yields two acetyl-CoA).

Key Intermediates and Enzymes

• Intermediates: Citrate, isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate, malate, oxaloacetate.

• Enzymes: Each step is catalyzed by a specific enzyme, e.g., citrate synthase, isocitrate dehydrogenase.

• Example: Isocitrate dehydrogenase catalyzes the first oxidative decarboxylation, producing NADH and CO2.

Energy Yield and Carbon Accounting

• CO2 Production: Two CO2 molecules are released per cycle turn (steps 3 and 4).

• NADH and FADH2: Each cycle produces 3 NADH and 1 FADH2.

• ATP/GTP: One molecule is produced per cycle via substrate-level phosphorylation.

• Example: For each glucose, the citric acid cycle yields 6 NADH, 2 FADH2, and 2 ATP (or GTP).

ELECTRON TRANSPORT CHAIN (ETC) AND OXIDATIVE PHOSPHORYLATION

Overview of the ETC

The electron transport chain is a series of protein complexes in the inner mitochondrial membrane that transfer electrons from NADH and FADH2 to oxygen, generating a proton gradient used to synthesize ATP.

• Main Complexes:

  1. Complex I (NADH: ubiquinone oxidoreductase)

  2. Complex II (succinate dehydrogenase)

  3. Complex III (cytochrome bc1 complex)

  4. Complex IV (cytochrome c oxidase)

• Mobile Carriers: Ubiquinone (CoQ), cytochrome c

• Proton Gradient: Electron transfer is coupled to proton pumping across the inner membrane, creating an electrochemical gradient.

• ATP Synthase: Uses the proton gradient to drive ATP synthesis from ADP and inorganic phosphate.

Electron Carriers and Redox Reactions

• NAD+/NADH: NAD+ is reduced to NADH during catabolic reactions; NADH donates electrons to Complex I.

• FAD/FADH2: FAD is reduced to FADH2 in the citric acid cycle; FADH2 donates electrons to Complex II.

• Cytochromes: Proteins with heme groups that undergo reversible oxidation and reduction.

• Example: The flow of electrons from NADH through the ETC ultimately reduces O2 to H2O.

ATP Yield from Oxidative Phosphorylation

• ATP per NADH: Approximately 2.5-3 ATP molecules are generated per NADH oxidized.

• ATP per FADH2: Approximately 1.5-2 ATP molecules are generated per FADH2 oxidized.

• Total ATP: Complete oxidation of one glucose molecule yields about 30-32 ATP.

• Example: The "processing" of 10 acetyl-CoA molecules through the citric acid cycle and ETC yields about 100 ATP.

Key Reactions and Equations

• Hydrolysis of ATP:

$\text{ATP} + \text{H}_2\text{O} \rightarrow \text{ADP} + \text{P}_i$

• Reduction of NAD+:

$\text{NAD}^+ + 2\text{e}^- + 2\text{H}^+ \rightarrow \text{NADH} + \text{H}^+$

• Reduction of FAD:

$\text{FAD} + 2\text{e}^- + 2\text{H}^+ \rightarrow \text{FADH}_2$

TABLE: Key Intermediates and Electron Carriers

Intermediate/Carrier	Function	Associated Complex
NADH	Electron donor	Complex I
FADH2	Electron donor	Complex II
CoQ (Ubiquinone)	Mobile electron carrier	Between Complexes I/II and III
Cytochrome c	Mobile electron carrier	Between Complexes III and IV
O2	Final electron acceptor	Complex IV

ADDITIONAL INFO

• High-Energy Phosphate Bonds: ATP contains two high-energy phosphoanhydride bonds; hydrolysis releases significant free energy.

• Vitamin Cofactors: Many electron carriers (e.g., NAD+, FAD) are derived from B vitamins (niacin, riboflavin).

• Proton Motive Force: The electrochemical gradient of protons across the inner mitochondrial membrane drives ATP synthesis.