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Oxidative Phosphorylation: The major energy provider of the cell

There are a lot of different ways organisms acquire food. Just think about how sharks, bees, plants, and bacteria eat. Almost all aerobic organisms (organisms that require oxygen to live) use oxidative phosphorylation, in one way or another, to produce the basic energy currency of the cell needs to function: ATP (adenosine triphosphate). Oxidative phosphorylation is the fourth step of cellular respiration, and produces the most of the energy in cellular respiration.
Where does oxidative phosphorylation fit into cellular respiration?
  1. Glycolysis, where the simple sugar glucose is broken down, occurs in the cytosol.
  2. Pyruvate, the product from glycolysis, is transformed into acetyl CoA in the mitochondria for the next step.
  3. The citric acid cycle, where acetyl CoA is modified in the mitochondria to produce energy precursors in preparation for the next step.
  4. Oxidative phosphorylation, the process where electron transport from the energy precursors from the citric acid cycle (step 3) leads to the phosphorylation of ADP, producing ATP. This also occurs in the mitochondria.

What is oxidative phosphorylation?

Oxidative phosphorylation is the process where energy is harnessed through a series of protein complexes embedded in the inner-membrane of mitochondria (called the electron transport chain and ATP synthase) to create ATP. Oxidative phosphorylation can be broken down into two parts: 1) Oxidation of NADH and FADHstart text, end text, start subscript, 2, end subscript, and 2) Phosphorylation.
Figure of the electron transport chain (complexes 1-4)

1. Oxidation of NADH and FADHstart text, end text, start subscript, 2, end subscript - losing electrons via high energy molecules

Step 1
Oxidative phosphorylation starts with the arrival of 3 NADH and 1 FADHstart text, end text, start subscript, 2, end subscript from the citric acid cycle, which shuttle high energy molecules to the electron transport chain. NADH transfers its high energy molecules to protein complex 1, while FADHstart text, end text, start subscript, 2, end subscript transfers its high energy molecules to protein complex 2. Shuttling high energy molecules causes a loss of electrons from NADH and FADHstart text, end text, start subscript, 2, end subscript, called oxidation (other molecules are also capable of being oxidized).
The opposite of oxidation is reduction, where a molecule gains electrons (which is seen in the citric acid cycle). Here’s an easy way to remember which process gains or loses electrons:
LEO the lion says GER
Lose Electrons Oxidation (LEO)
Gain Electrons Reduction (GER)
Figure of oxidation of NADH and FADH2
Step 2 - Hitting the gym to pump some serious hydrogens
The process of NADH oxidation leads to the pumping of protons (single positively-charged hydrogen atoms denoted as Hstart superscript, start text, plus, end text, end superscript) through protein complex 1 from the matrix to the intermembrane space. The electrons that were received by protein complex 1 are given to another membrane-bound electron carrier called ubiquinone or Q.
This process of transferring electrons drives the pumping of protons, which is seen as unfavorable. Electron transfer driving proton pumping is repeated in complexes 3 and 4 (which we will discuss in steps 2 - 5). As this action is repeated, protons will accumulate in the intermembrane space. This accumulation of protons is how the cell temporarily stores transformed energy.
Note - FADHstart text, end text, start subscript, 2, end subscript has a slightly different route than NADH. After its arrival at protein complex 2, its high energy electrons are directly transferred to Q, to form reduced Q, or QHstart text, end text, start subscript, 2, end subscript. There is no hydrogen pumping for the exchange of the FADHstart text, end text, start subscript, 2, end subscript electrons here.
Figure of electrons being transferred from FADH2 and NADH to ubiquinone
Step 3
The rest of the steps are now the same for the high energy molecules from NADH and FADHstart text, end text, start subscript, 2, end subscript in earlier steps. Inside the nonpolar region of the phospholipid bilayer, UQHstart text, end text, start subscript, 2, end subscript (which is also a nonpolar compound) transports the electrons to protein complex 3. UQHstart text, end text, start subscript, 2, end subscript also carries protons. When UQHstart text, end text, start subscript, 2, end subscript delivers electrons to protein complex 3, it also donates its protons to be pumped.
Figure of UQH2 transporting electrons to protein complex 3
Step 4
The electrons that arrived at protein complex 3 are picked up by cytochrome C (or “cyt C”), the last electron carrier. This action also causes protons to be pumped into the intermembrane space.
Figure electrons being transferred from protein complex 3 to cytochrome C
Step 5
Cytochrome C carries the electrons to the final protein complex, protein complex 4. Once again, energy released via electron shuttling allows for another proton to be pumped into the intermembrane space. The electrons are then drawn to oxygen, which is the final electron acceptor. Its important to note that oxygen must be present for oxidative phosphorylation to occur. Water is formed as oxygen receives the electrons from protein complex 4, and combines with protons on the inside of the cell.
Figure of cytochrome C carrying electrons to protein complex 2
In summary
  • +3 NADH
  • +1 FADHstart text, end text, start subscript, 2, end subscript
  • +3 Hydrogen protons (Hstart superscript, start text, plus, end text, end superscript)
  • -2 Hydrogen protons (Hstart superscript, start text, plus, end text, end superscript)
  • -½ Ostart text, end text, start subscript, 2, end subscript
  • +1 Hstart text, end text, start subscript, 2, end subscriptO

2. Phosphorylation - the production of ATP

Step 6
As a result of part 1 (Oxidation of NADH and FADHstart text, end text, start subscript, 2, end subscript), an electrochemical gradient is created, meaning there is a difference in electrical charge between the two sides of the inner mitochondrial membrane. The outside, or exterior, of the mitochondrial membrane is positive because of the accumulation of the protons (Hstart superscript, start text, plus, end text, end superscript), and the inside is negative due to the loss of the protons. A chemical concentration gradient has also developed on either side of the membrane. The electrochemical gradient is how the cell transfers the stored energy from the reduced NADH and FADHstart text, end text, start subscript, 2, end subscript.
Figure showing electrochemical gradient
Step 7
When there is a high concentration of protons on the outside of the mitochondrial membrane, protons are pushed through ATP synthase. This movement of protons causes ATP synthase to spin, and bind ADP and Pi, producing ATP. Finally, ATP is made!
In summary
  • -ADP
  • -Pi
  • +ATP
Figure of protons being pushed through mitochondrial membrane producing ATP

Consider the following:

In oxidative phosphorylation, oxygen must be present to receive electrons from the protein complexes. This allows for more electrons and high energy molecules to be passed along, and maintains the hydrogen pumping that produces ATP. What happens if we run out of oxygen? How do we break down our food to make energy? The body has a plan B for this situation called fermentation. It happens all the time in athletes, like runners, when they use all their oxygen and produce lactic acid. Fermentation starts after glycolysis, replacing the citric acid cycle and oxidative phosphorylation. During glycolysis, only two ATP molecules are produced. NADH is then oxidized to transform the pyruvates made in glycolysis into lactic acid.

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