For any reaction to be thermodynamically feasible, it is necessary that it involves a negative change in Gibb’s free energy, which ultimately becomes the underlying driving force behind the spontaneity of all the chemical reactions. But considering ATP, an energy rich molecule indispensable to life, its synthesis is not thermodynamically feasible i.e. it is a non-spontaneous reaction or in other words, energy is required for it to be synthesized. The very next question which arises in our minds is that, “Who provides the energy for ATP synthesis?” The answer to this, is the Electron Transport Chain (ETC). The Electron transport chain (ETC) comprises of a series of red-ox reactions, which involve the constant shuttling of electrons between a series of electron donors and acceptors in a sequential manner which ultimately leads to the formation of an electrochemical gradient, which, upon harnessing leads to the production of ATP. In simple words, ETC is nothing but a relay, where, the mobile electron carriers are the participants of the race, and electrons- the baton. The final acceptor of electrons in this relay race, is molecular oxygen, which is reduced to water. (In case of anaerobic respiration, there can be a variety of terminal electron acceptors). NADH and FADH2 being the by products of most catabolic reactions are used to transport electrons in the form of hydride ions to a series of membrane bound electron carriers and is ultimately passed on to molecular oxygen i.e. oxidation of NADH and FADH2 is brought about by a series of four different protein complexes (labelled 1-4 and ATP synthase). A complex is nothing but a molecule or a protein, which is surrounded by other proteins. These 4 protein complexes and ATP synthase are together associated with mobile electron carriers. Yet again, we do not really need so many different protein complexes to transfer electrons right? This can also happen in a single step, which would lead to faster and more efficient synthesis of ATP, right? But this is not found in nature, the reason why all the protein complexes and the shuttling of electrons between them is so important is because the energy released due to oxidation of glucose is huge i.e.. 2880kJ/mol. Picking up such a huge amount of energy at once by the cell would not only cause damage to the cell but also there would be a great loss in energy. Therefore this energy is released with the help of a number of electron carriers and complexes which lead to release of energy in a slow and sequential manner, thereby maximizing the usage of glucose. The electron carriers are often arranged in increasing order of electronegativity, so that electrons can be passed efficiently. This entire process takes place in the inner membrane of the mitochondria in eukaryotes. An interesting feature about the ETC, is that it is present in multiple copies, the inner mitochondrial membrane.

Complex I (NADH-coenzyme Q oxidoreductase):
NADH binds to the very first complex of the ETC by interacting with the prosthetic group Flavin Mono-nucleotide (FMN) and thereby acts as a reducing agent to reduce Coenzyme Q10, itself undergoing rapid oxidation to produce NAD. Thus, NAD is recycled. Along with the two electrons that FMN picks up to undergo reduction, it also receives the hydrogen ion, coming from NADH. In addition to all this, it also picks up a proton from the matrix. The electrons are next moved to the FeS clusters and the protons are forced into the inter-membrane space. So what would happen if these protons are not pumped into the inter-membrane space? The answer to this is extremely simple, electron transfer would not occur, vice-versa also being true. The transfer of protons and electrons are interlinked, the events must happen together, or not at all.

Complex II (Succinate-Q oxidoreductase). 
This complex forms a second entry point into the electron transport chain using the succinate which is an intermediate metabolite of the TCA cycle to yield fumarate and FADH2. The electrons are welcomed by FAD, which gets reduced to FADH2 and passes the electrons to Ubiquinone. Complex 2 is a parallel electron transport pathway to complex 1, but unlike complex 1, no protons are transported to the inter-membrane space in this pathway. Therefore, the pathway through complex 2 contributes less energy to the overall electron transport chain process.Electrons pass from complex I to a carrier (Coenzyme Q) embedded by itself in the membrane. From Coenzyme Q electrons are passed to a complex III which is associated with another proton translocation event. Note that the path of electrons is from Complex I to Coenzyme Q to Complex III. Complex II, the succinate dehydrogenase complex, is a separate starting point, and is not a part of the NADH pathway.

Q (Ubiquinone/ ubiquinol): Ubiquinone receives electrons from several different electron carriers and gets reduced. Upon reduction, it passes the electrons to complex III.

Complex III (Q-cytochrome c oxidoreductase).
This complex accomplishes the oxidation of ubiquinol and the reduction of two molecules of cytochrome-c. Four hydrogens are pumped across the membrane to the inter-membrane space.

Complex IV (Cytochrome c oxidase):
Finally the electrons are transferred to oxygen and two protons are pumped across the membrane. i.e. 10 protons are pumped across membrane per molecule of NADH. Molecular oxygen is diatomic and hence two pairs of electrons are required along with two cytochrome oxidase complexes to complete the reaction. This steps is of significance as it ensures the continuous removal of electrons from the system.

So what would happen if molecular oxygen was not present at this stage to accept electrons? Obviously, there would have been no outlet for electrons . A similar situation arises during the premature leakage of electrons from the electron complexes. Such a leakage of electrons is commonly observed from complex I which generates a number of reactive oxygen species such as the superoxide radical. In many aerobic cells, the ETC are the most important source of ROS. It is estimated that under physiological oxygen concentrations, only 1-3% of the oxygen reduced in the mitochondria may form the superoxide anion. This low rate of leakage is probably due to the arrangement of electron carriers into complexes that facilitate the movement of electrons to the next component of the chain rather than directly to oxygen. This is also one of the reasons why the presence of different electron carriers and the shuttling of electrons between them becomes so important.

Cyanide as an inhibitor: Cyanide is a chemical compound that contains monovalent combining group -CN. Carbon is triply bonded to nitrogen atom. Cyanide has the potential of binding to cytochrome c oxidase i.e. Complex IV of the ETC. -CN attacks the iron present in the complex, thereby inhibiting cytochrome c oxidase to show its normal activity. Its binding is so tight, that no electrons and oxygen can then be bound to cytochrome c oxidase.Electron transport is reduced to zero. Thus it blocks the ETC and inhibits the protons from moving into the matrix of the mitochondria. The proton gradient is disturbed and ATP synthesis is halted.

ATP Synthase:
This complex makes use of the proton potential created by ETC. By transporting a proton down the gradient, it brings about the phosphorylation of ADP to ATP. Current model of its action utilizes the binding charge mechanism and it appears that part of this large protein complex accomplishes a mechanical rotation in the process of phosphorylation and release of the ATP molecule. So part of its action is like a molecular motor.

Thus the problem of ATP synthesis is solved, thanks to the Electron Transport Chain.