Biochemistry, Electron Transport Chain

Article Author:
Maria Ahmad
Article Editor:
Chadi Kahwaji
10/27/2018 12:31:33 PM
PubMed Link:
Biochemistry, Electron Transport Chain


The electron transport chain is a series of protein complexes that couple redox reactions, creating an electrochemical gradient that leads to the creation of ATP. It occurs in both cellular respiration and photosynthesis. In the former, the electrons come from breaking down organic molecules and energy is released. In the latter, the electrons enter the chain after being excited by light, and the energy released is used to build carbohydrates.


Aerobic cellular respiration made up of 3 parts: glycolysis, the Krebs cycle, and oxidative phosphorylation. In glycolysis, glucose is metabolized into 2 molecules of pyruvate, with an output of ATP and nicotinamide adenine dinucleotide (NADH). The pyruvate is oxidized into acetyl CoA and NADH and carbon dioxide (CO2). The acetyl CoA is then used in the Krebs cycle, also known as the citric acid cycle, which is a chain of chemical reactions that produce CO2, NADH, flavin adenine dinucleotide (FADH2), and ATP. In the final step, the NADH, FADH2 amassed from the previous steps is used in oxidative phosphorylation, to make water and ATP.

Oxidative phosphorylation is made up of 2 parts: the electron transport chain (ETC) and chemiosmosis. The ETC is a collection of proteins and organic molecules, which electrons pass through in a series of redox reactions, and release energy. The energy released forms a proton gradient, which is used in chemiosmosis to make a large amount of ATP.

Photosynthesis is a metabolic process that converts light energy into chemical energy, to build sugars. In the light-dependent reactions, light energy and water are used to make ATP, NADPH, and oxygen (O2). The proton gradient used to make the ATP is formed via an electron transport chain. In the light-independent reactions, sugar is made from the ATP and NADPH from the previous reactions.


In the electron transport chain (ETC), the electrons go through a chain of proteins that increases its reduction potential and causes a release in energy. Some steps across the electron transport chain use this energy to pump a hydrogen ion (H+) from the matrix to the intermembrane space of the mitochondria and create a proton gradient. This increases the acidity in the intermembrane space and creates an electrical difference with positive charge outside and a negative charge inside. The electrons are reduced along the ETC through the following proteins, consecutively: complex I, complex II, coenzyme Q, complex 2, cytochrome C and cytochrome IV.

  • Complex I, also known as ubiquinone oxidoreductase (NADH), is made up of FMN and eight iron-sulfur containing proteins (Fe-S) and contains the enzyme NADH dehydrogenase. The NADH is oxidized, and the electrons are transferred from NADH to coenzyme Q while translocating a proton across the membrane. Complex I may play an important role in causing apoptosis in programmed cell death.[1]
  • Complex II, also known as succinate dehydrogenase, accepts hydrogens from FADH2. Like complex I, it is connected to ubiquinone, which connects to complex III. Complex II gains electrons from FADH2 and passes it down to Coenzyme Q. No proton is translocated across the membrane by complex II, and less ATP is produced with this pathway.
  • Coenzyme Q, also known as ubiquinone, is made up of a quinone and a hydrophobic tail. Its purpose is to function as an electron carrier and transfer electrons to complex III. Coenzyme Q can be reduced to semiquinone (partially reduced, radical form) and ubiquinol (fully reduced) through the Q cycle. Ubiquinone is reduced to ubiquinol with the addition of electrons from complex I and II. Subsequently, ubiquinol is oxidized back to ubiquinone by cytochrome b in complex III. This redox reaction of coenzyme Q allows the transfer of electrons.
  • Complex III is made up of cytochrome b, Fe-S protein, Rieske center, and cytochrome c proteins. The iron ion core is reduced and oxidized as electrons pass through it. Cytochrome c accepts electrons from ubiquinone and passes them to complex IV while pumping protons across the membrane.[2]
  • Complex IV is reduced by cytochrome c and transfers the electrons to oxygen, the final electron carrier in aerobic cellular respiration. The cytochrome proteins c, a, and a3 hold the oxygen until it is completely reduced, and once it is, the oxygen picks up 2 hydrogen ions and forms water. The free energy from the electron transfer causes 4 protons to move into the mitochondrial matrix. Oxygen is reduced as in the following reaction:
    • 2 e- + H+ + ½ O2 -> H2O

ATP synthase uses the proton gradient across the mitochondrial membrane to form ATP. It is made up of F0 and F1 subunits which act as a rotational motor system. F0 portion is embedded in the mitochondrial membrane and is protonated and deprotonated repeatedly causing it to rotate. This rotation catalyzes the formation of ATP from ADP and Pi. The F1 portion works to hydrolyze the ATP.[3]


Nicotinamide adenine dinucleotide has two forms: NAD+ (oxidized) and NADH (reduced). It is a dinucleotide connected by phosphate groups. One nucleoside has an adenine base and the other nicotinamide. When involved in metabolic redox reactions, the reaction is as follows:

  • Reaction 1: RH2 + NAD+ -> H+ + NADH + R

With R being the reactant, for example, sugar.

NADH enters the ETC at complex I and produces a total of 3 ATP. When NADH is oxidized, it is broken into NAD+, H+, and 2 e-.

  • Reaction 2: NADH -> H+ +  NAD+ + 2 e-

Nicotinamide adenine dinucleotide phosphate’s 2 forms are NADP+ (oxidized) and NADPH (reduced). NADPH, found in plants, is produced at the end of the photosynthetic light reactions, and as a reducing agent, helps convert CO2 into glucose in the Calvin cycle.

Flavin adenine dinucleotide has 4 redox states, 3 of them being FAD (quinone, fully oxidized form), FADH- (semiquinone, partially oxidized), and FADH2 (hydroquinone, fully reduced). FAD is made up of an adenine nucleotide and a flavin mononucleotide (FMN), connected by phosphate groups. FAD is a highly stable aromatic ring, and FADH2 is not, so when FADH2 is oxidized it becomes aromatic and releases energy. This makes FAD a strong oxidizing agent, with an even more positive reduction potential than NAD+. FADH2 enters the ETC at complex II and creates a total of 2 ATP. FADH2 creates less ATP because the electrons it donates are at a lower energy state.

  • Reaction 3: FADH2 -> FAD +  2 H+ + 2 e-

Clinical Significance

Aspirin (Salicylic Acid)

Salicylic acid is an uncoupler. An uncoupler dissociates the electron transport from phosphorylation preventing the formation of ATP. Salicylic acid acts as an uncoupler because it serves as a proton carrier from the intermembrane space to the mitochondrial matrix. The proton is transferred without the use of ATP synthase, and no ATP is produced. Aspirin poisoning can lead to uncoupling and hyperthermia by a loss of energy in heat from the ETC rather than being transferred to production of ATP.[4]

ETC Inhibitors

Certain poisons can inhibit the ETC such as rotenone, carboxin, antimycin A, cyanide, carbon monoxide (CO), sodium azide, and oligomycin. Rotenone inhibits complex I, carboxin inhibits complex II, antimycin A inhibits complex III, cyanide and CO inhibit complex IV, and oligomycin inhibits ATP synthase.[5][6]