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Electron transport chain (ETC) and its mechanism

During cellular respiration, ATP is produced by the citric acid cycle and glycolysis.
During cellular respiration, ATP is produced by the citric acid cycle and glycolysis. During aerobic catabolism of glucose, the majority of ATP is not generated from these pathways directly. The electron transport chain is derived primarily from the movement of electrons through electron transporters in response to redox reactions. Hydrogen ions are therefore accumulated in the matrix. A concentration gradient is formed when hydrogen ions diffuse out of the matrix space after passing through ATP synthase. The catalytic action of ATP synthase is catalyzed by hydrogen ions, which phosphorylate ADP to generate ATP.

As far as glucose metabolism is concerned, only oxygen from the atmosphere is involved in the electron transport chain. Plants continuously take in oxygen; animals take it in through their respiratory system. In electron transport, electrons are rapidly transferred from one component to another, to the point where they reduce molecular oxygen, producing water at the end of the chain. As illustrated in the Figure that is given right below, there are four protein-based complexes, referred to as complexes I through IV. When these four complexes are aggregated, along with the associated mobile electron carriers, an electron transport chain is formed. Multi-copy electron transport chains are found in the mitochondria and plasma membranes of eukaryotes and prokaryotes respectively. However, prokaryotes that live in anaerobic conditions may not need oxygen for electron transport. A proton pump across a membrane is a common characteristic of all electron transport chains.

Complex I

The first complex aboard NADH is reached by two electrons. It consists of a flavin mononucleotide (FMN) molecule and a protein containing iron and sulfur (Fe-S). The electron transport chain consists of several prosthetic groups or co-factors, including FMN, derived from vitamin B2, also called riboflavin. An enzyme's ability to function depends on non-protein molecules called prosthetic groups. A prosthetic group consists of an organic or inorganic non-peptide molecule attached to a protein; a prosthetic group includes a coenzyme, which is like an enzyme's prosthetic group. It consists of 45 amino acid chains, is very large, and is called NADH dehydrogenase. By pumping four hydrogen ions across the mitochondrial membrane from the matrix, Complex I establishes and maintains a hydrogen gradient between the two compartments.

Q and Complex II

FADH2 is directly received by complex II, which does not go through complex I. It is ubiquinone (Q) that connects the first and second complexes. As a lipid-soluble molecule, Q can freely pass through the hydrophobic core of membranes. In the electron transport chain, electrons delivered from ubiquinone (QH2) to the next complex occur after it has been reduced by the electron transport chain (QH2). The electrons from complexes I and II, including succinate dehydrogenase, are obtained by Q from NADH and FADH2, respectively. A small complex is formed by this enzyme and FADH2 passes electrons directly from this enzyme to the electron transport chain. By bypassing the proton pump, the FADH2 electrons do not energize it, and so fewer ATP molecules are produced. As the inner mitochondrial membrane is pumped with protons, the amount of ATP molecules obtained ultimately is directly proportional.

Complex III

Due to its combination of cytochrome b, another Fe-S protein, and two Rieske centers (2Fe-2S centers), it is also called cytochrome oxidoreductase. The prosthetic group of heme is present in cytochrome proteins. While heme molecules are similar to hemoglobin heme molecules, heme molecules carry electrons rather than oxygen. Consequently, the iron ion passes through different oxidation states as it passes electrons, including Fe++ (reduced) and Fe+++ (oxidized). Each complex of cytochromes has slightly different properties because of the different proteins that bind to its heme molecules. The third complex pumps protons across the membrane, while the fourth complex transports electrons from the third complex to cytochrome c (cytochrome c accepts electrons from Q, but Q can only accept one electron at a time).

Complex IV

Cytochrome proteins a, c, and a3 are part of the fourth complex. A pair of copper ions (CuA) and a copper ion (CuB) are included in this complex, as are two heme groups. The cytochromes retain the oxygen molecule firmly between the iron and copper ions once the oxygen has been reduced fully. Water (H2O) is then produced by reducing oxygen and grabbing two hydrogen ions from the surrounding medium. A chemiosmotic process uses an ion gradient induced by hydrogen ions being removed from the system.


During chemiosmosis, hydrogen ions (protons) are pumped across a membrane by using the free energy generated by redox reactions. Because hydrogen ions aggregate on one side of the membrane because of their positive charges, the uneven distribution of hydrogen ions across the membrane causes an electrochemical gradient (hence, a concentration gradient).

If the membrane were open to hydrogen ions diffusing across it, they would tend to diffuse back across it due to their electrochemical gradients. The nonpolar regions of phospholipid membranes are unable to diffuse many ions without help from ion channels. The inner mitochondrial membrane and the matrix space need to be permeable to hydrogen ions through ATP synthase. By diffusing hydrogen ions through it down an electrochemical gradient, this complex protein is used as a miniature generator. The hydrogen ion gradient provides the potential energy for this molecular machine, which helps phosphate to be added to ADP and ATP to be formed.

During aerobic glucose metabolism, 90% of ATP is made by chemiosmosis, which is used to capture solar energy. Oxidative phosphorylation is the process by which mitochondria produce ATP by chemiosmosis. Through these reactions, electrons are removed from hydrogen atoms, and ATP is produced as a result. At the beginning of this process, glucose molecules contained these atoms. An oxygen molecule is reduced to oxygen ions using electrons at the end of the pathway. Water is formed when hydrogen ions (protons) are attracted to oxygen by excess electrons.

ATP yield

Catabolism of glucose produces varying amounts of ATP molecules. Hydrogen ions can be transported through membranes differently depending on species, for example. Electrons shuttled across mitochondrial membranes are another source of variance. So, electrons are collected by NAD+ or FAD+ inside the mitochondria (NADH from glycolysis is not readily absorbed by the mitochondria). Since these FAD+ molecules are less capable of transporting ions, fewer ATP molecules are produced when they are acting as a carrier. The liver utilizes NAD+ for electron transport, while the brain utilizes FAD+.

The fact that intermediate molecules in these pathways are used in other processes also affects the yield of ATP molecules produced from glucose. A problem arises due to the interaction of glucose catabolism with pathways that are involved in the synthesis and degradation of all other biochemical compounds in cells, making the situation far more complex than the perfect scenario described thus far. The glycolytic pathway is fed with sugars other than glucose to obtain energy. Furthermore, nucleic acids are formed from five-carbon sugars formed during glycolysis. Nonessential amino acids cannot be made by glycolysis or the citric acid cycle. The pathways involved in this process break down amino acids and triglycerides for energy, and intermediates that are converted into lipids like cholesterol and triglycerides. A living system takes about 34 percent of its energy from glucose through glucose catabolism.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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