• Introduction
  • The basics of oxidative phosphorylation
  • The electron transport chain
  • Complex I
  • Complex II & Ubiquinone
  • Complex III
  • Complex IV
  • Chemiosmosis
  • ATP yield
  • 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

Aerobic respiration is a combination of complex interconnected pathways that break down glucose into adenosine triphosphate (ATP). With sufficient amounts of oxygen present, this process consists of glycolysis, the citric acid cycle, and oxidative phosphorylation.

Each phase has its own function that allows a glucose molecule to be fully broken down. After a glucose molecule is fully oxidized, it produces 36 molecules of ATP. This energy is then used during exercise and maintaining regular bodily functions such as breathing, heartbeat, cell repair, hormonal activity, etc.

Oxidative phosphorylation is the third and final phase of cellular respiration. It utilizes the end products of both glycolysis and the citric acid cycle to produce 32-34 molecules of ATP.

This post explains the basics of oxidative phosphorylation and why it is so crucial for living organisms. 

The basics of oxidative phosphorylation

Oxidative phosphorylation is the final phase of cellular respiration and takes place in the mitochondria. This phase can be divided into two stages; 

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

Oxidative phosphorylation begins with the end products of glycolysis and the citric acid cycle, NADH and FADH₂. These two compounds are electron carriers that have the capacity to produce energy by carrying electrons to the electron transport chain. 

The electron transport chain is made up of four protein complexes. Each of them gradually releases energy that is used to pump hydrogen ions (H+) out of the mitochondrial matrix into the intermembrane space. This flow of protons generates an outward current, creating an electrical potential across the membrane. The difference in charge between the two sides of the mitochondrial membrane creates an electrochemical gradient, known as a proton-motive force. Then, the hydrogen ions diffuse from a higher concentration to a lower concentration carrying electrical potential. 

As these ions flow back through the mitochondrial membrane, they catalyze an enzyme called ATP synthase that phosphorylates (adds a phosphate group) ADP, producing ATP. This whole process of transporting hydrogen ions across a semipermeable membrane to generate ATP is called chemiosmosis. 

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Oxidative Phosphorylation

The final phase of cellular respirationNADH & FADH₂ release their electrons to the electron transport chainAerobic processTakes place in the mitochondriaProduces 28 ATP

Electron transport chain

The electron transport chain is a series of protein complexes that oxidizes high-energy electron carriers NADH and FADH₂, forcing them to release their electrons. Then, these electrons are passed from one complex to another and they gradually release energy. 

There are four complexes in total, labeled from I to IV;

  • Complex I picks up the electrons from NADH and reduces it to NAD+. This process also releases four hydrogen ions (H+) from the mitochondrial matrix into the intermembrane space, establishing an electrochemical gradient.
  • Complex II receives FADH₂, bypassing the first complex and delivering electrons directly into the electron transport chain. Ubiquinone (Q), a mobile carrier that can freely travel through the mitochondrial membrane, receives the electrons from complexes I and II and delivers them to complex III. 
  • Complex III also pumps protons through the mitochondrial membrane. It also passes electrons to cytochrome c, another mobile carrier able to pass through the membrane, which delivers them to complex IV.
  • Complex IV receives electrons from cytochrome c and passes them to oxygen, which is the final acceptor in the electron transport chain. Then, oxygen picks up two hydrogen ions from the surrounding medium to form water. If oxygen is not present, the electron transport will stop working and ATP cannot be produced aerobically. 

The energy released in the electron transport chain is also used to pump out a total of 10 hydrogen ions across the mitochondrial membrane. Because of the hydrogen ions’ positive charge and higher concentration on one side of the membrane, an electrochemical gradient is created. This is ultimately what powers ATP production. 

If you want to learn more about the electron transport chain and what happens during complexes I-IV, check out this post.

Chemiosmosis

The oxidation of NADH and FADH₂ releases hydrogen ions, or protons, which creates 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, owing to the H+ ions’ higher concentration and positive charge on one side of the membrane.

Then, these hydrogen ions flow from a higher concentration to a lower concentration through the membrane back into the mitochondrial matrix. This flow of protons also drives an enzyme called ATP synthase, which works like a tiny battery. 

ATP synthase catalyzes a reaction that adds an inorganic phosphate (Pi) to ADP, producing ATP. This whole process in which the energy from the hydrogen ion gradient is used to generate ATP is called chemiosmosis. The electron transport chain and chemiosmosis are collectively known as oxidative phosphorylation, which accounts for nearly 90% of all ATP produced during aerobic glucose catabolism.

The hydrogen ions released in the electron transport chain create an electrochemical gradient that drives the production of ATP.

ATP Yield

Cellular respiration produces 30-32 molecules of ATP for every molecule of glucose. Two net ATP (or GTP) is produced during glycolysis and two during the citric acid cycle. The remaining ATP molecules are produced during oxidative phosphorylation. 

Recent studies have estimated that four hydrogen ions must diffuse back into the mitochondrial matrix through the ATP Synthase to produce one molecule of ATP. Since each NADH pumps out a total of 10 hydrogen ions into the intermembrane space, a single NADH produces 2.5 molecules of ATP. On the other hand, FADH₂, which enters the electron transport chain in complex II, only pumps out a total of 6 hydrogen ions. This produces 1.5 molecules of ATP.

For every glucose molecule, cellular respiration produces a maximum of 10 NADH and 2 FADH₂. Therefore, oxidative phosphorylation produces a total of 28 molecules of ATP. And, since four ATP molecules were produced in glycolysis and the citric acid cycle, the theoretical maximum yield of a single glucose molecule is 32 ATP. 

Phase

Products

ATP Yield

Glycolysis

2 ATP
2 NADH

2 ATP
3-5 ATP

Pyruvate Oxidation

2 NADH

5 ATP

The Citric Acid Cycle

2 ATP/GTP
6 NADH
2 FADH2

2 ATP
15 ATP
3 ATP

Total

30-32 ATP

One thing to note is that glycolysis takes place in the cytoplasm whereas the electron transport chain is located in the mitochondria. Since NADH cannot freely move through the mitochondrial membrane, it must shuttle its electrons into the mitochondria. Once there, these electrons are passed to NAD+ or FAD. Because these electron carriers have a different ATP yield, the total amount of ATP produced ranges from 30 to 32. 

Oxidative phosphorylation oxidizes NADH & FADH₂ and phosphorylates ADP to form ATP.

Final thoughts

As you can see, oxidative phosphorylation is an incredibly intricate process that may seem impossible to fully comprehend. Therefore, it is no surprise Peter D. Mitchell, the discoverer of the chemiosmotic principle was awarded a Nobel prize in chemistry in 1978. 

Oxidative phosphorylation is the final phase of cellular respiration. Due to its high ATP yield, it is also a crucial stage in overall energy metabolism and life in general. It utilizes the electron carriers released via glycolysis and the citric acid cycle to pump hydrogen ions out of the mitochondrial membrane. This fuels the synthesis of ATP from ADP and phosphate (Pi). The final products of this process are ATP and water. 

Did you learn anything new about oxidative phosphorylation? Let us know in the comments. 

Sources

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    Energy Metabolism