top of page

ETC and Oxidative Phosphorylation

ETC or Electron Transport Chain refers to the series of electron carriers present in a membrane through which electron flows. This flow of electron through the electron carriers is responsible for creating a proton gradient required for the formation of ATP.

Mitochondria, which is the major site of ATP formation depends on the ETC. The electron carriers are embedded in the Inner Mitochondrial Membrane in the form of enzyme complexes. The enzyme complexes are :-

  • Complex I- NADH dehydrogenase

  • Complex II- Succinate dehydrogenase

  • Complex III- Cytochrome b-c1 complex or cytochrome c reductase

  • Complex IV- Cytochrome a-a3 complex or cytochrome c oxidase

  • Complex V- ATP synthase

These enzyme complexes oxidize the NADH+(H+) and FADH produced in the mitochondrial matrix during Tricarboxylic acid cycle (TCA cycle). This oxidation releases the electrons which flows through the enzyme complexes.

The flow of electrons from one enzyme complex to another is facilitated by mobile electron carriers present in the membrane. These mobile electron carriers are:-

  1. Ubiquinone (UQ)/ Coenzyme Q- lipid soluble, freely diffusible in lipid bilayer.

  2. Cytochrome c- soluble protein towards peri-mitochondrial side.



The complex I is a large L-shaped enzyme complex and consist of several groups like FMN (flavin mononucleotide) and multiple Fe-S centers.

NADH dehydrogenase performs two processes:-

1) Oxidizes the NADH+H+ from the matrix side which releases 2 electrons and 2 protons. These 2 electrons and protons are captured by Ubiquinone (UQ) which gets reduced into Ubiquinol (UQH2).

2) Also acts as a proton pump and uses the energy of electrons to transfer 4H+ from the matrix (N-side) to peri-mitochondrial space (P-side).

Overall reaction:-

NADH+ 5H+(N-side) + Q ----> NAD+ +QH2 + 4H+(P-side)

The reduced UQH2 diffuses from complex I to complex III and gets oxidized to UQ.


The complex II is the only membrane bound enzyme of the TCA cycle. It consist of 3 Fe-S centers, a bound FAD and a Succinate binding site towards the matrix.

The Succinate is oxidized to Fumarate during the TCA cycle and it transfers 2 electrons and 3 protons to the FAD bound to Succinate dehydrogenase. This reduces FAD into FADH2 which further transfers these electrons and protons to UQ and reduces it into UQH2.

Overall reaction:-

FADH2 + UQ -----> FAD + UQH2

The reduced UQH2 diffuses from complex II to complex III and gets oxidized to UQ.


The cytochrome bc1 complex consist of a Cyt b group, 2 Fe-S centers and a Cyt c1 group.

It receives electrons from the UQH2 reduced by complex I and II and oxidizes it to UQ. These electrons are then transferred through cyt b--FeS--cyt c1 and ultimately reduces two molecules of Cyt c.

During this flow of electrons, two protons are pumped from matrix (N-side) to the peri-mitochondrial space (P-side) and two protons are released by the reduced UQH2 to the peri-mitochondrial space. As a result, oxidation of one UQH2 results in transfer of 4 H+ from N-side to P-side.

Overall reaction:-

UQH2 + 2 cyt c (oxidized) + 2H+(N-side) ----> UQ + 2 cyt c (reduced) + 4H+ (P-side)

The reduced Cyt c after getting reduced moves to the Complex IV.


The complex IV consists of two Cytochromes- Cyt a and Cyt a3 along with two Copper centers CuA and CuB. The oxidation of two Cyt c releases two electrons which are transferred to CuA-Cyt a-Cyt a3- CuB. These electrons are finally accepted by the terminal electron acceptor of the ETS i.e. O2 which gets reduced into H2O.

The complex IV also acts as a proton pump and transfers 2H+ from matrix (N-side) to peri-mitochondrial space (P-side) during the flow of 2 electrons from Cyt c to O2.

Overall reaction:-

2 cyt C (reduced) + 4H+ (N-side) + O2 ---- 2 cyt c (oxidized) + 2H+ (P-side) + H2O


1. Oxidation of one NADH+H+

Complex I---> Complex III---> Complex IV---> O2

  • Complex I- 4H+

  • Complex II- Not involved

  • Complex III- 4H+

  • Complex IV- 2H+

Total= 10 H+ from matrix to peri-mitochondrial space

2. Oxidation of one FADH2

Complex II---> Complex III---> Complex IV---> O2

  • Complex I- Not involved

  • Complex II- Zero

  • Complex III- 4H+

  • Complex IV- 2H+

Total= 6 H+ from matrix to peri-mitochondrial space

3. Reduction of each molecule of O2 into H2O by 2 electrons released either from NADH+H+ or FADH2 removes 2H+ from the matrix in the form of H2O.


The proton gradient created by the flow of electrons through the ETS creates a Proton motive force which has two components:-

(1) the chemical potential energy due to the difference in concentration of protons in the two regions separated by the membrane

(2) the electrical potential energy that results from the separation of charge

The ATP synthase consist of two parts: F1 and F0. The F1 part has the ATP synthase enzymatic activity while the F0 part creates a channel for facilitated diffusion of H+.

When the proton gradient breaks, the proton motive force is used for the formation of high energy bond between ADP and Pi to form ATP.

For formation of one ATP, 4H+ must flow from peri-mitochondrial space to matrix through the F0 pat of ATP synthase.

Therefore, net ATP gain from oxidation of:

1 NADH+H+ = 10/4 = 2.5 ATP

1 FADH2= 6/4 = 1.5 ATP


70 views0 comments

Recent Posts

See All



bottom of page