Cellular Respiration: Glycolysis, TCA Cycle, Redox Potentials, and Chemiosmotic Coupling

Overview

Cellular respiration is the process by which cells degrade biomolecules to generate energy in a usable form, primarily ATP. This process involves several interconnected metabolic pathways, including glycolysis, the TCA (Krebs) cycle, and oxidative phosphorylation. Understanding these pathways is essential for grasping how cells extract energy from carbohydrates, fats, and proteins.

Breakdown of Food: Entry Points into Cellular Respiration

Catabolism of Major Biomolecules

• Carbohydrates are broken down into simple sugars (e.g., glucose), which enter glycolysis.

• Fats are hydrolyzed into fatty acids, which undergo β-oxidation to form Acetyl-CoA.

• Proteins are degraded into amino acids, which can be converted into intermediates that enter the TCA cycle or glycolysis.

All three macronutrients ultimately converge at Acetyl-CoA, which enters the TCA cycle for further oxidation.

Cellular Respiration: Pathways and Overall Reaction

Main Stages

• Glycolysis: Occurs in the cytosol; converts glucose to pyruvate.

• TCA Cycle (Krebs Cycle): Occurs in the mitochondrial matrix; oxidizes Acetyl-CoA to CO2 and generates high-energy electron carriers.

• Oxidative Phosphorylation: Occurs in the mitochondrial inner membrane; uses electron carriers to drive ATP synthesis.

Overall Reaction:

Glycolysis

Phases of Glycolysis

Glycolysis is divided into two main phases: the preparatory (investment) phase and the payoff phase.

Preparatory (Investment) Phase

• Glucose is phosphorylated and rearranged to form fructose-1,6-bisphosphate.

• This phase consumes 2 ATP molecules per glucose.

• Key enzyme: Phosphofructokinase-1 (PFK-1), which is highly sensitive to ATP levels and acts as the rate-limiting step.

Payoff Phase

• Fructose-1,6-bisphosphate is split and converted to pyruvate.

• This phase produces 4 ATP and 2 NADH per glucose.

• Net products: 2 ATP, 2 NADH, and 2 pyruvate per glucose.

Summary Table: Glycolysis Inputs and Outputs

Regulation of Glycolysis

• Phosphofructokinase-1 (PFK-1) is inhibited by high ATP and activated by low ATP, ensuring glycolysis proceeds when energy is needed.

Anaerobic Glycolysis

• In the absence of oxygen, pyruvate is converted to lactate (lactic acid) to regenerate NAD+ for continued glycolysis.

• This process is important in muscle cells during intense exercise.

Pyruvate Oxidation and Entry into the TCA Cycle

Conversion to Acetyl-CoA

• Pyruvate is transported into the mitochondria and converted to Acetyl-CoA by the pyruvate dehydrogenase complex.

• This reaction produces one NADH and one CO2 per pyruvate.

TCA Cycle (Krebs Cycle, Citric Acid Cycle)

Purpose and Steps

The TCA cycle oxidizes Acetyl-CoA to CO2, generating high-energy electron carriers (NADH and FADH2) for use in oxidative phosphorylation.

• Each turn of the cycle produces 3 NADH, 1 FADH2, and 1 GTP (or ATP).

• Key intermediates include citrate, isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate.

Summary Table: TCA Cycle Outputs (per Acetyl-CoA)

Redox Potentials and Electron Transport Chain

Redox Potentials

• Redox potential measures the tendency of a chemical species to acquire electrons and be reduced.

• Electrons move spontaneously from pairs with low redox potential (e.g., NADH/NAD+) to pairs with high redox potential (e.g., O2/H2O).

Electron Transport Chain (ETC)

• Located in the mitochondrial inner membrane.

• NADH and FADH2 donate electrons to the ETC, which are passed through a series of complexes (I-IV).

• Electron flow drives the pumping of protons (H+) from the matrix to the intermembrane space, creating an electrochemical gradient.

Proton-Motive Force and Chemiosmotic Coupling

Generation of Proton-Motive Force

• The ETC establishes a proton gradient (higher H+ concentration in the intermembrane space than in the matrix).

• This gradient creates both a membrane potential and a pH difference (ΔpH).

Proton-motive force equation:

ATP Synthesis via Chemiosmotic Coupling

• Protons flow back into the mitochondrial matrix through ATP synthase, driving the synthesis of ATP from ADP and inorganic phosphate.

• This process is known as chemiosmotic coupling.

• Approximately 32-38 ATP molecules are produced per molecule of glucose oxidized.

Additional Info: Uncouplers

• Chemicals like 2,4-dinitrophenol (DNP) can dissipate the proton gradient, preventing ATP synthesis and releasing energy as heat.

Summary Table: ATP Yield from Cellular Respiration

Key Terms

• Glycolysis: The metabolic pathway that converts glucose to pyruvate, generating ATP and NADH.

• TCA Cycle (Krebs Cycle): A series of reactions that oxidize Acetyl-CoA to CO2 and generate electron carriers.

• Redox Potential: A measure of the tendency of a molecule to gain electrons.

• Proton-Motive Force: The electrochemical gradient of protons across the mitochondrial membrane.

• Chemiosmotic Coupling: The process by which the proton gradient drives ATP synthesis.