ELECTRON TRANSPORT CHAIN: COMPONENTS, SEQUENCE, INHIBITORS - BIOLOGY - 2025

The electron transport chain consists of a set of protein molecules and coenzymes within a membrane. As its name indicates, it is responsible for the transport of electrons from the coenzymes NADH or FADH2 to the final receptor that is O2 (molecular oxygen).

In this transport process, the energy released when the electrons are transferred from the coenzymes to the molecular oxygen through redox centers attached to proteins, is associated with the production of energy (ATP). This energy is obtained thanks to the proton gradient that is generated in the inner mitochondrial membrane.

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This transport system is made up of various components that can be found in at least two oxidation states. Each of them is effectively reduced and reoxidized during the movement of electrons from NADH or FADH2 to O2.

The coenzymes NAD + and FAD are reduced in the fatty acid oxidation pathways and the citric acid cycle as a consequence of the oxidation of various substrates. These coenzymes are subsequently oxidized in the electronic transport chain.

So the electronic transport system consists of a sequence of oxidation-reduction reactions that are connected to each other.

Chain components

Depending on the type of organism, 3 to 6 components can be observed constituting the electron transport chain. The process of electron transport and the synthesis of ATP by oxidative phosphorylation, are processes that occur in a membrane.

In the case of prokaryotic cells (aerobic bacteria), these processes occur associated with the plasma membrane. In eukaryotic cells it occurs in the mitochondrial membrane, so the components of electron transport are found in the inner part of the membrane.

Electrons are transferred gradually through four complexes that make up the electronic transport chain.

Each complex has several protein components associated with prosthetic groups (non-amino acid components of conjugated proteins) redox, which allow their reduction potentials to increase.

In addition, this transport system is composed of various molecular species such as flavoproteins; coenzyme Q also called ubiquinone (CoQ or UQ); various cytochromes such as cytochrome b, c, c1, a and a3; proteins with Fe-S groups and proteins attached to Cu. These molecules bind to the membrane, with the exception of cytochrome c.

Complex I

Complex I called NADH coenzyme quinone oxidoreductase, or NADH dehydrogenase, is made up of about 45 polypeptide chains and contains one flavin mononucleotide (FMN) molecule and eight to nine Fe-S clusters. As its name implies, this complex transfers a pair of electrons from the coenzyme NADH to CoQ.

The function of the NADH dehydrogenase complex begins with the binding of NADH to the complex on the matrix side of the inner mitochondrial membrane. The electrons are then transported from NADH to the FMN. Subsequently, the electrons pass from the reduced flavin (FMNH2) to the Fe-S proteins.

FMNH2 works as a kind of bridge between NADH and Fe-S proteins, since the latter can only transfer a single electron, while the coenzyme NADH transfers two, so that flavins carry out this transfer of a single electron thanks to to its redox state of semiquinone.

Finally, electrons are transferred from the Fe-S clusters to coenzyme Q, which is a mobile electron carrier with an isoprenoid tail that makes it hydrophobic, allowing it to cross the center of the mitochondrial membrane.

Complex II

Complex II, better known as succinate dehydrogenase, is an integral protein of the inner mitochondrial membrane, and is an enzyme that intervenes in the citric acid cycle.

This complex is composed of two hydrophilic and two hydrophobic subunits with heme b groups that provide the binding site for CoQ, in addition to a flavoprotein and a protein with Fe-S.

In the citric acid cycle (Krebs or tricarboxylic acid cycle), succinate is converted to fumarate by succinate dehydrogenase, reducing the coenzyme FAD to FADH2. From this last coenzyme, the electrons are transferred to the Fe-S centers which in turn transfer them to CoQ.

During the reactions of this electron transfer, the standard redox potential is very low, which prevents the free energy needed to synthesize ATP from being released.

This means that complex II is the only complex in the electron transport chain incapable of providing energy for ATP synthesis. However, this complex is key in the process, since it transfers the electrons from FADH2 to the rest of the chain.

Complex III

Complex III, cytochrome bc1 complex or CoQ cytochrome c reductase, transfers electrons from reduced coenzyme Q to cytochrome c. This transfer occurs through a single redox pathway, known as the Q cycle.

This complex consists of a protein with Fe-S and three different cytochromes, in which the iron atom located in the heme group varies cyclically between the reduced (Fe2 +) and oxidized (Fe3 +) states.

Cytochromes are electron transport hemoproteins, which possess redox activity. They are present in all organisms, except for some obligate anaerobes.

These proteins have heme groups that alternate between two oxidation states (Fe2 + and Fe3 +). Cytochrome c is a mobile electron carrier weakly associated with the inner membrane of mitochondria.

The cytochromes found in this complex are cytochromes b, c and a, all 3 are redox active proteins with hae groups with different characteristics, which alternate their oxidation states between Fe2 + and Fe3 +.

Cytochrome c is a peripheral membrane protein that functions as an electron "shuttle" with cytochrome c1 and complex IV.

Complex IV

Cytochrome c and O2 are the final receptors for electrons derived from the oxidation of organic material, so complex IV or cytochrome c oxidase is the terminal enzyme in the electron transport process. This accepts electrons from cytochrome c and transfers them to the O2 reduction.

The function of the complex is to catalyze oxidations of one electron of the four consecutive molecules of reduced cytochrome c, that is, it simultaneously reduces four electrons of one molecule of O2, finally producing two molecules of H2O.

Electron transport sequence

Electrons are transferred from complexes I and II to complex III thanks to coenzyme Q, and from there they pass to complex IV through cytochrome c. As the electrons pass through these four complexes, they increase the reduction potential, releasing energy, which is then used for the synthesis of ATP.

In total, the transfer of a pair of electrons causes the translocation of 10 protons through the membrane; four in complexes I and IV and two in complex III.

NADH dehydrogenase

This enzyme catalyzes the oxidation of coenzyme NADH by coenzyme Q. Electrons move from NADH to FMN which is attached to the hydrophilic tail of complex I. Clusters of Fe-S transfer electrons one at a time. These Fe-S groups reduce CoQ, which is embedded in the membrane, to ubiquinol (reduced CoQ).

During the transfer of electrons to CoQ, four protons are in turn transferred through the inner membrane to the intermembrane space. The mechanism by which these protons are translocated involves proteins located in the hydrophobic tail of complex I.

The electron transfer process in this step releases free energy, specifically -16.6 kcal / mol.

CoQ-cytochrome c reductase and Cycle Q

Coenzyme Q is oxidized by cytochrome c, in a reaction catalyzed by this coenzyme. The oxidation of ubiquinol (reduced CoQ) occurs at a certain site of the complex (Qo or oxidation site) in the mitochondrial membrane, transferring two electrons, one to the protein with the Fe-S groups and the other to the heme groups.

In the Q cycle, the oxidation of CoQ produces semiquinone, which is where electrons are transferred to the heme groups b1 and bh. As this electron transfer occurs, a second CoQ is oxidized at the Qo site, repeating the cycle.

This cycle causes the transfer of two electrons and in turn the translocation of four protons to the intermembrane space, with the release of -10.64 kcal / mole of free energy.

Cytochrome c oxidase

This enzyme (complex IV) catalyzes the oxidation of cytochrome c (reduced) by O2, which is the final electron acceptor. This transfer produces one H2O molecule for each pair of electrons transferred in addition to the translocation of protons through the membrane.

The electrons move one by one, from the reduced cytochrome c to a pair of CuA ions, then pass to a heme group and finally reach the binuclear center of the complex containing CuB ions and heme a3, where the transfer of four electrons occurs up to oxygen.

In complex IV the elements transfer electrons one by one, so that O2 is gradually reduced, so that the release of some toxic compounds such as superoxide, hydrogen peroxide or hydroxyl radicals does not occur.

The energy released in this stage corresponds to -32 kcal / mol. The electrochemical gradient generated during the transfer process and the energy changes (ΔE) caused by a pair of electrons as they pass through the four complexes, corresponds, at each stage, to the free energy required for the production of an ATP molecule.

Succinate dehydrogenase

As mentioned, this complex has the sole but important function of introducing the electrons of FADH2 from the citric acid cycle to the electron transport chain.

This enzyme catalyzes the oxidation of coenzyme FADH2 by coenzyme Q (oxidized). In the citric acid cycle, as succinate is oxidized to fumarate, two electrons and two protons are transferred to the FAD. Subsequently, FADH2 transfers these electrons to CoQ through the Fe-S centers of the complex.

Finally, from CoQ the electrons are transferred to complex III, following the steps described above.

The complexes of the chain are independent

The four complexes that make up the electronic transport chain are independent, that is, they are found and operate independently in the inner mitochondrial membrane, and the movement of each of them in the membrane does not depend on or is linked to the other complexes.

Complexes I and II move in the membrane, transferring their electrons to CoQ, which also diffuses in the membrane and transfers them to complex III, from where the electrons pass to cytochrome c, which is also mobile in the membrane and deposits the electrons in complex IV.

Inhibitors of the electronic transport chain

Some specific inhibitors act on the electronic transport chain that interfere in its process. Rotenone is a commonly used insecticide that binds stoichiometrically to complex I, preventing the reduction of CoQ.

Some barbiturate-type drugs, such as Piericidin and Amytal, inhibit complex I, interfering with the transfer of electrons from the Fe-S groups to CoQ.

In complex II, some compounds such as thenoyltrifluoroacetone and malonate act as competitive inhibitors with succinate, preventing its oxidation and, in turn, the transfer of electrons to the FAD.

Some antibiotics, such as myxothiazol and stigmatellin, bind to the Q binding sites of CoQ, inhibiting the transfer of electrons from coenzyme Q to the Fe-S centers of proteins.

Cyanide, azide (N3-), sulfuric acid, and carbon monoxide inhibit complex IV. These compounds bind to heme groups, preventing the transfer of electrons to the binuclear center of the complex or to oxygen (O2).

By inhibiting the electron transport chain, energy production is stopped by oxidative phosphorylation, causing serious damage and even death to the body.

References

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