• Introduction
  • The basics of oxidative phosphorylation
  • The electron transport chain
  • Complex I
  • Complex II & Ubiquinone
  • Complex III
  • Complex IV
  • What happens to the released hydrogen ions?
  • Final thoughts
  • Sources
  • Chemiosmosis: the movement of ions across a semipermeable membrane down their electrochemical gradient
  • Electron carrier: Small organic molecules that switch between oxidized and reduced forms and transport electrons during metabolic reactions
  • FADH₂: Also known as Flavin adenine dinucleotide. It is an electron carrier that transports electrons from glycolysis and the citric acid cycle to the electron transport chain.
  • Heme group: an organic ring-like molecule containing an iron (Fe) molecule
  • NADH: A reduced form of Nicotinamide adenine dinucleotide that carries electrons from one reaction to another. An important cofactor in metabolism consisting of two nucleotides and their phosphate groups
  • Oxidation: a molecule loses electrons
  • Oxidative phosphorylation: Formation of ATP via the transfer of electrons from NADH or FADH2 to O2 by a series of electron carriers
  • Prosthetic group: a nonprotein component required for the biological function of a protein.
  • Reduction: a molecule gains electrons

Introduction

The electron transport chain (ETC) is part of oxidative phosphorylation, where electron carriers NADH and FADH₂, the end products of glycolysis and the citric acid cycle, are oxidized to generate adenosine triphosphate (ATP). This can be divided into two phases; 

  • Oxidation of NADH and FADH₂
  • Phosphorylation of ADP to ATP

The electron transport chain is responsible for the oxidation process, whereas phosphorylation is a result of chemiosmosis. Both of these processes take place in the mitochondria and require oxygen to work.

This post explains the basic function of the electron transport chain and its complexes.

The basics of the electron transport chain

The electron transport chain consists of four protein complexes, each of which has a specific function in transferring electrons from NADH and FADH₂ to oxygen. 

  • Complex I picks up the electrons from NADH and reduces it to NAD+, as well as releases four hydrogen ions (H+) from the mitochondrial matrix into the intermembrane space. This establishes an electrochemical gradient.
  • Complex II receives FADH₂, which bypasses the first complex and delivers electrons directly into the electron transport chain. Ubiquinone (Q), a carrier that can freely travel through the membrane, receives the electrons from complexes I and II and delivers them to complex III. This complex does not pump protons into the intermembrane space. 
  • Complex III pumps out four hydrogen ions into the intermembrane space. It also passes electrons to cytochrome c, another carrier with the ability to move through the membrane, which transfers them to complex IV.
  • Complex IV receives electrons from cytochrome c and transfers them to oxygen – the final acceptor in the electron transport chain. Then, oxygen picks up two hydrogen ions from the surrounding medium and forms water. Note that without oxygen, the electron transport will stop working and ATP cannot be produced aerobically. 

The released hydrogen ions produce an outward current, creating electrical potential across the mitochondrial membrane. The difference in current between the two sides of the membrane creates an electrochemical gradient, also known as a proton-motive force. Then, these ions diffuse from higher to lower concentration back into the mitochondrial matrix, carrying electrical potential.

This movement of hydrogen ions powers an enzyme called ATP synthase, which phosphorylates ADP and produces ATP. But before we jump too far ahead, let’s take a closer look at what happens in each complex. 

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Electron Transport Chain


The oxidative phase of oxidative phosphorylationOxidizes NADH & FADH₂Aerobic processTakes place in the mitochondriaPumps out hydrogen ions into the intermembrane spaceCreates a hydrogen ion gradient

Complex I

Complex I consists of flavin mononucleotide (FMN) and an iron-sulfur (Fe-S) -containing protein. FMN is derived from vitamin B₂, also known as riboflavin. It is also one of many prosthetic groups in the electron transport chain.

A prosthetic group is a non-amino acid component required for the biological function of a protein. These non-peptide molecules can be organic (such as vitamins, sugars, or lipids) or inorganic (such as metal ions). Prosthetic groups also include coenzymes, because they are prosthetic groups of enzymes.

In complex I, the catalyzing enzyme is NADH dehydrogenase – one of our largest membrane-bound proteins consisting of 46 amino acid chains. This complex has two main functions; transferring electrons from NADH to ubiquinone and pumping out hydrogen ions across the mitochondrial matrix into the intermembrane space.

This process begins when FMN strips NADH from its two electrons and delivers them down a chain of iron-sulfur clusters. Then, these electrons are placed on a ubiquinone molecule which carries them to the next complex in the electron transport chain. This process releases four protons across the membrane for every molecule of NADH, which establishes and maintains an electrochemical gradient that powers ATP synthase.

Complex II & Ubiquinone

Complex II, succinate dehydrogenase, plays an interesting role in mitochondrial metabolism. It is the same enzyme that was also used in the citric acid cycle to transform succinate into fumarate in the process of producing FADH₂. Together, succinate dehydrogenase and FADH₂ form a small complex that bypasses the first complex and transfers electrons directly into the electron transport chain. Unlike complex I, complex II does not pump out hydrogen ions into the intermembrane space.

Ubiquinone (Q) is a compound that ties complexes I and II to complex III. It is lipid-soluble and can freely move through the hydrophobic core of the mitochondrial membrane. After ubiquinone is reduced to ubiquinol (QH₂), it releases its electrons to the next complex in the electron transport chain.

Ubiquinone receives electrons from two sources:

  1. From NADH derived from complex I
  2. From FADH₂ derived from complex II

Since the electrons provided by FADH₂ bypass the first complex, they do not participate in pumping out hydrogen ions into the intermembrane space. Because the total ATP yield is directly related to the number of hydrogen ions released, fewer ATP molecules are generated from FADH₂.

Complex III

Complex III is also known as Q-cytochrome c oxidoreductase. It consists of three subunits:

  1. Cytochrome c, which contains a single prosthetic heme group.
  2. Cytochrome b, which contains two prosthetic heme groups.
  3. The Rieske center, which contains the 2Fe-2S center.

Cytochrome proteins contain a prosthetic heme group. A heme molecule is similar to hemoglobin but carries electrons instead of oxygen. This also means that the iron ion at its core is reduced and oxidized as it donates and accepts electrons. Thus, it fluctuates between oxidized (Fe3+) and reduced (Fe2+states during the electron transport process. Because the heme molecules in the cytochromes are bound to different proteins, they have different characteristics. This is also what makes each complex of the electron transport chain.

Cytochrome c is a unique electron transport protein because it is not a part of a larger complex. Thus, it is free to diffuse through the inner mitochondrial membrane. Cytochrome c is the acceptor of electrons from ubiquinone. However, while Q carries electrons in pairs, cytochrome c can only accept one of them at a time. This process of transferring electrons from ubiquinol to cytochrome c is called the Q cycle.

In addition to passing electrons to cytochrome c for transport to the fourth complex, complex III also pumps out four hydrogen ions across the mitochondrial membrane.

Complex IV

Complex IV, also known as cytochrome c oxidase, is a multiunit structure that transfers electrons from cytochrome c to oxygen. It is composed of three cytochrome proteins; c, a, and a3. The complex contains two heme groups (one in each cytochromes a and a3) as well as three copper ions (two CuA and one CuB in cytochrome a3).

These cytochromes hold an oxygen molecule between the iron and copper ions. After the oxygen is reduced, it picks up two hydrogen ions from the surrounding medium and produces water (H₂O).

Complex IV also pumps out two hydrogen ions out of the mitochondrial matrix into the intermembrane space, further contributing to the electrochemical gradient. This gradient is used in the process of chemiosmosis to synthesize ATP.

The hydrogen ions released in the electron transport chain create an electrochemical gradient that powers ATP synthase.

What happens to the released hydrogen ions?

The released hydrogen ions, or protons, create an outward current across the mitochondrial membrane. The difference in charge between the two sides of the membrane creates an electrochemical gradient known as the proton-motive force. Through simple diffusion, these hydrogen ions flow from a higher concentration to a lower concentration back into the mitochondrial matrix. This flow of electrons also powers an enzyme called ATP synthase, which works like a tiny generator. 

ATP synthase catalyzes the addition of a phosphate (Pi) to ADP which produces ATP. This entire process in which the energy from the proton gradient is used to generate ATP is called chemiosmosis. Together, the electron transport chain and chemiosmosis are called oxidative phosphorylation. This accounts for roughly 90% of all ATP produced during the breakdown of glucose in cellular respiration.

Final thoughts

The electron transport chain is an incredibly complex mechanism – and a crucial one for living organisms. Luckily, unless you are majoring in biology, you only need to know the basics.

In short, the electron transport chain oxidizes electron carriers NADH and FADH₂, releasing them from their electrons. This process also pumps hydrogen ions into the intermembrane space which creates a hydrogen ion gradient. This gradient is what ultimately drives the phosphorylation of ADP to ATP.

Did you learn anything new about the electron transport chain? Let us know in the comments.

Sources

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