Metabolic Pathways: Catabolic Pathways and Cellular Respiration (Chapter 9: Concepts 9.1–9.5)

Metabolic Pathways

Introduction to Catabolic Pathways

Catabolic pathways are essential metabolic routes that break down complex molecules into simpler ones, releasing energy that cells can use for work. The primary example in eukaryotic cells is cellular respiration, which converts glucose and other organic fuels into ATP.

• Catabolism: The breakdown of molecules to release energy.

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

• Redox reactions: Chemical reactions involving the transfer of electrons; oxidation is the loss of electrons, reduction is the gain of electrons.

• ATP (Adenosine Triphosphate): The main energy currency of the cell.

Example: Cellular respiration is a catabolic pathway that breaks down glucose to produce ATP.

Glycolysis

9.2 Glycolysis Oxidizes Glucose to Pyruvate

Glycolysis is the first stage of cellular respiration, occurring in the cytosol. It converts one molecule of glucose (6 carbons) into two molecules of pyruvate (3 carbons each), generating ATP and NADH.

• Location: Cytosol

• Phases:

  • Energy Investment Phase (Steps 1–5): 2 ATP are used to phosphorylate glucose and its intermediates.

  • Energy Payoff Phase (Steps 6–10): 4 ATP and 2 NADH are produced; glucose is split into two pyruvate molecules.

• Net Inputs and Outputs:

  • Glucose + 2 ATP + 4 ADP + 2 NAD+ → 2 Pyruvate + 2 H2O + 4 ATP + 2 NADH + 2 H+

  • Net gain: 2 ATP, 2 NADH per glucose

• No carbon is lost as CO2 during glycolysis.

• Occurs with or without O2. If oxygen is present, pyruvate proceeds to aerobic respiration.

Equation:

$\text{Glucose} + 2\,\text{NAD}^+ + 2\,\text{ADP} + 2\,\text{P}_i \rightarrow 2\,\text{Pyruvate} + 2\,\text{NADH} + 2\,\text{ATP} + 2\,\text{H}_2\text{O}$

Pyruvate Oxidation and the Citric Acid Cycle

9.3 Pyruvate is Oxidized and Transferred to the Citric Acid Cycle

After glycolysis, pyruvate is transported into the mitochondrion and converted into acetyl CoA by the pyruvate dehydrogenase complex. This process links glycolysis to the citric acid cycle.

• Steps in Pyruvate Oxidation:

  1. Removal of the carboxyl group from pyruvate, releasing CO2.

  2. Oxidation of the remaining 2-carbon fragment to acetate, reducing NAD+ to NADH.

  3. Attachment of coenzyme A (derived from vitamin B) to acetate, forming acetyl CoA.

• Products per pyruvate: 1 CO2, 1 NADH, 1 acetyl CoA

Equation:

$\text{Pyruvate} + \text{NAD}^+ + \text{CoA} \rightarrow \text{Acetyl CoA} + \text{NADH} + \text{CO}_2$

9.3 The Citric Acid Cycle (Krebs Cycle, TCA Cycle)

The citric acid cycle completes the breakdown of glucose by oxidizing acetyl CoA to CO2. It occurs in the mitochondrial matrix and generates NADH, FADH2, and ATP (or GTP).

• Main Functions:

  • Generates 1 ATP (or GTP) per cycle via substrate-level phosphorylation

  • Transfers most energy to NADH and FADH2

  • Produces CO2 as a waste product

• Key Electron Carriers:

  • NAD+ (oxidized) / NADH (reduced)

  • FAD (oxidized) / FADH2 (reduced)

• 8 Main Steps:

  1. Acetyl CoA (2C) combines with oxaloacetate (4C) to form citrate (6C).

  2. Citrate is converted to isocitrate (isomerization).

  3. Isocitrate is oxidized, reducing NAD+ to NADH and releasing CO2 (forms alpha-ketoglutarate, 5C).

  4. Alpha-ketoglutarate is oxidized, reducing NAD+ to NADH, releasing another CO2, and forming succinyl CoA (4C).

  5. Succinyl CoA is converted to succinate, producing GTP (can be used to make ATP).

  6. Succinate is oxidized to fumarate, reducing FAD to FADH2.

  7. Fumarate is converted to malate by addition of water.

  8. Malate is oxidized to oxaloacetate, reducing NAD+ to NADH.

• Total Yield per Glucose (2 cycles): 6 NADH, 2 FADH2, 2 ATP (or GTP), 4 CO2

Equation (per glucose):

$2\,\text{Acetyl CoA} + 6\,\text{NAD}^+ + 2\,\text{FAD} + 2\,\text{ADP} + 2\,\text{P}_i \rightarrow 4\,\text{CO}_2 + 6\,\text{NADH} + 2\,\text{FADH}_2 + 2\,\text{ATP}$

The Electron Transport Chain (ETC)

9.4 The Pathway of Electron Transport

The electron transport chain is a series of protein complexes embedded in the inner mitochondrial membrane. It uses electrons from NADH and FADH2 to pump protons and generate a proton gradient, ultimately producing ATP via oxidative phosphorylation.

• Location: Inner mitochondrial membrane

• Function: Transfers electrons from NADH and FADH2 to oxygen, forming water

• Sequential Redox Reactions: Each complex accepts electrons from its neighbor with lower electronegativity

• Key Components:

  • Complex I: Accepts electrons from NADH via FMN (flavin mononucleotide)

  • Complex II: Accepts electrons from FADH2

  • Ubiquinone (Q): Mobile electron carrier

  • Cytochromes: Proteins with heme groups that transfer electrons

  • Oxygen: Final electron acceptor, forms water

• ATP Yield: Glycolysis and citric acid cycle yield 4 ATP per glucose via substrate-level phosphorylation; most ATP is produced by oxidative phosphorylation in the ETC.

Equation:

$\text{NADH} + \text{FADH}_2 + O_2 + ADP + P_i \rightarrow \text{NAD}^+ + \text{FAD} + H_2O + ATP$

Electron Transport Chain Steps

• Electrons from NADH enter at complex I; electrons from FADH2 enter at complex II (lower energy level).

• Electrons are passed through FMN, iron-sulfur proteins, ubiquinone, and cytochromes.

• Cytochromes transfer electrons to oxygen, which picks up protons to form water.

• Proton gradient generated across the membrane powers ATP synthase to produce ATP.

Example: The ETC is responsible for the majority of ATP production in aerobic respiration.

Summary Table: ATP and Electron Carrier Yield per Glucose

Stage	ATP Produced	NADH Produced	FADH2 Produced	CO2 Produced
Glycolysis	2	2	0	0
Pyruvate Oxidation	0	2	0	2
Citric Acid Cycle	2	6	2	4
Total (Substrate-level)	4	10	2	6

Additional info: Most ATP is generated by oxidative phosphorylation, not substrate-level phosphorylation. The theoretical maximum yield is about 30–32 ATP per glucose.