ELECTRON TRANSPORT CHAIN biochemistry med

1. Introduction

The Electron Transport Chain (ETC), also known as the respiratory chain, is one of the most critical biochemical systems in all living organisms that depend on oxygen. It serves as the final stage of aerobic cellular respiration, the process by which cells convert the chemical energy in nutrients into a usable form of energy known as adenosine triphosphate (ATP).

Without the ETC, cells could not efficiently harvest energy from carbohydrates, fats, and proteins. The chain works by passing electrons from reduced electron carriers (NADH and FADH₂) through a series of protein complexes embedded in the inner mitochondrial membrane. With each step, energy is released, which is then used to pump protons across the membrane. This establishes a proton gradient—often referred to as the proton motive force—which powers ATP synthase to generate ATP.

In short: the ETC is where most of our ATP comes from, and therefore it sustains life.

2. Historical Perspective

The study of cellular respiration began in the 19th century, but it wasn’t until the mid-20th century that the ETC was fully understood. Early researchers like Otto Warburg demonstrated that respiration was linked to redox reactions. In the 1960s, Peter Mitchell proposed the chemiosmotic hypothesis, suggesting that ATP synthesis was driven not by a high-energy chemical intermediate (as many thought at the time) but by a gradient of protons across the mitochondrial membrane. Initially controversial, his theory was later confirmed experimentally and earned him the Nobel Prize in Chemistry in 1978.

This historical journey highlights how the ETC is not just a biological system but also a milestone in scientific discovery.

3. Overview of Cellular Respiration & Placement of ETC

Before diving into the ETC itself, it’s important to see where it fits into the bigger picture of metabolism. Cellular respiration can be broken into four main stages:

Glycolysis – occurs in the cytoplasm; glucose (6 carbons) is broken down into two molecules of pyruvate (3 carbons each). Net yield: 2 ATP and 2 NADH.

Pyruvate Oxidation – pyruvate enters the mitochondrion and is converted into acetyl-CoA, producing NADH and CO₂.

Citric Acid Cycle (TCA/Krebs Cycle) – acetyl-CoA enters a cycle that generates NADH, FADH₂, ATP (or GTP), and releases CO₂.

Electron Transport Chain & Oxidative Phosphorylation – NADH and FADH₂ donate electrons to the ETC. The electrons pass through a chain of complexes, leading to ATP production via oxidative phosphorylation.

The ETC is the final step, and although it doesn’t produce ATP directly (ATP synthase does that), without it the entire respiration process would grind to a halt.

4. Structure of the Mitochondria & Its Role in ETC

The ETC takes place in the inner mitochondrial membrane. Mitochondria are double-membraned organelles:

Outer Membrane: relatively permeable to small molecules due to porins.

Inner Membrane: highly impermeable, folded into structures called crista

1. ELECTRON TRANSPORT CHAIN DR. PARIHA OBHAYO LECTURER BIOCHEMISTRY SSCMS

2. LEARNING OBJECTIVES Introduction Importance Overview Steps and complexes

3. Cellular respiration

4. Introduction The Electron Transport Chain (ETC) is the final stage of cellular respiration. It occurs in the inner mitochondrial membrane . Main role: to transfer electrons from reduced coenzymes ( NADH, FADH₂ ) to oxygen , forming water. During this process, a proton gradient is generated across the membrane. This gradient powers ATP synthesis (oxidative phosphorylation).

5. Importance of ETC Produces the majority of ATP in aerobic organisms. Links the breakdown of carbohydrates, fats, and proteins to energy production. Essential for maintaining cellular energy balance . Defects can cause serious metabolic and mitochondrial diseases .

6. Overview of ETC ETC has four protein complexes (I–IV) + two mobile carriers ( CoQ , Cytochrome c). Electrons flow in a stepwise manner . Oxygen is the final electron acceptor . Proton pumping creates a proton motive force (PMF) .

7. Complex I – NADH Dehydrogenase Accepts electrons from NADH . Transfers them to Coenzyme Q ( CoQ ) . Pumps 4 H⁺ ions into intermembrane space.

8. Complex II – Succinate Dehydrogenase Accepts electrons from FADH₂ (from TCA cycle). Transfers them to CoQ . Does not pump protons .

9. Coenzyme Q (Ubiquinone) Small lipid-soluble carrier. Shuttles electrons from Complex I & II → Complex III . Complex III – Cytochrome bc ₁ Complex Transfers electrons from CoQ → Cytochrome c . Pumps 4 H⁺ ions into intermembrane space.

10. Cytochrome c Small soluble protein. Transfers electrons from Complex III → Complex IV . Complex IV – Cytochrome c Oxidase Transfers electrons to oxygen (O₂) → forms H₂O . Pumps 2 H⁺ ions into intermembrane space.

11. Proton Gradient & Chemiosmosis ETC creates a proton gradient (H⁺ ions in intermembrane space). Gradient drives ATP synthase to convert ADP + Pi → ATP . This process = Oxidative Phosphorylation .

12. Inhibitors of ETC Complex I → Rotenone, Amytal. Complex III → Antimycin A. Complex IV → Cyanide, CO. ATP synthase → Oligomycin. Uncouplers (e.g., DNP) → collapse proton gradient.

13. Role of Inhibitors in ETC ETC inhibitors block electron flow at specific complexes. This stops proton pumping , preventing formation of the proton gradient . As a result, ATP synthesis halts . Depending on site: Complex I (Rotenone, Amytal): Blocks NADH pathway. Complex III (Antimycin A): Stops transfer to Cytochrome c. Complex IV (Cyanide, CO): Prevents oxygen reduction → most lethal. ATP Synthase (Oligomycin): Stops ATP production despite intact gradient. Uncouplers (DNP, Thermogenin ): Allow protons to leak back, dissipating gradient → no ATP, but heat is produced.

14. Biological Oxidation In the electron transport chain, biological oxidation means the removal of electrons or hydrogen atoms from molecules inside the cell to release energy. Oxidation and Reduction Oxidation is when a molecule loses electrons or hydrogen, while reduction is when a molecule gains electrons or hydrogen. These two always occur together.

15. Redox Pair A redox pair is simply the oxidized and reduced form of the same molecule, such as NAD⁺ and NADH. Redox Potential Redox potential tells us how easily a molecule can accept or donate electrons. Molecules with a low redox potential (like NADH) readily donate electrons, while those with a high redox potential (like oxygen) are strong electron acceptors. In the ETC, electrons move from low to high redox potential, and this flow drives ATP production.

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