Question

a) Sketch a model for the electron-transport pathway in the mitochondrial inner membrane. Show the pathways of the electrons transport from the reduced forms of coenzyme in the mitochondrial electron-transport chain. What is the functional role of electron transport system in metabolism?

b) What is an uncoupler or uncoupling agent? Provide an example of an uncoupling agent.

Answer 1

a) The electron transport chain is the last component of aerobic respiration and is the only part of glucose metabolism that uses atmospheric oxygen. It is a series of redox reactions in which electrons are passed rapidly from one component to the next, to the endpoint of the chain where the electrons reduce molecular oxygen, producing water.

There are four complexes composed of proteins, complex I, II, III and IV and the aggregation of these four complexes, together with associated mobile, accessory electron carriers, is called the electron transport chain.

The electron transport chain is present in multiple copies in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes.The common feature of all electron transport chains is the presence of a proton pump to create a proton gradient across a membrane.

Complex I

To start, two electrons are carried to the first complex aboard NADH. This complex, is composed of flavin mononucleotide (FMN) and an iron-sulfur (Fe-S)-containing protein. FMN, which is derived from vitamin B2, also called riboflavin, is one of several prosthetic groups or co-factors in the electron transport chain.

The enzyme in complex I is NADH dehydrogenase and is a very large protein, containing 45 amino acid chains. Complex I can pump four hydrogen ions across the membrane from the matrix into the intermembrane space, and it is in this way that the hydrogen ion gradient is established and maintained between the two compartments separated by the inner mitochondrial membrane.

Q and Complex II

Complex II directly receives FADH2, which does not pass through complex I. The compound connecting the first and second complexes to the third is ubiquinone (Q). The Q molecule is lipid soluble and freely moves through the hydrophobic core of the membrane. Once it is reduced, (QH2), ubiquinone delivers its electrons to the next complex in the electron transport chain. Q receives the electrons derived from NADH from complex I and the electrons derived from FADH2 from complex II, including succinate dehydrogenase.

This enzyme and FADH2 form a small complex that delivers electrons directly to the electron transport chain, bypassing the first complex. Since these electrons bypass and thus do not energize the proton pump in the first complex, fewer ATP molecules are made from the FADH2 electrons. The number of ATP molecules ultimately obtained is directly proportional to the number of protons pumped across the inner mitochondrial membrane.

Complex III

This complex is composed of cytochrome b, another Fe-S protein, Rieske center (2Fe-2S center), and cytochrome c proteins; this complex is also called cytochrome oxidoreductase. Cytochrome proteins have a prosthetic group of heme. The heme molecule is similar to the heme in hemoglobin, but it carries electrons, not oxygen.

As a result, the iron ion at its core is reduced and oxidized as it passes the electrons, fluctuating between different oxidation states: Fe++ (reduced) and Fe+++ (oxidized). Complex III pumps protons through the membrane and passes its electrons to cytochrome c for transport to the fourth complex of proteins and enzymes.

Complex IV

The fourth complex is composed of cytochrome proteins c, a, and a3. This complex contains two heme groups (one in each of the two cytochromes, a, and a3) and three copper ions (a pair of CuA and one CuB in cytochrome a3).

The cytochromes hold an oxygen molecule very tightly between the iron and copper ions until the oxygen is completely reduced. The reduced oxygen then picks up two hydrogen ions from the surrounding medium to make water (H2O). The removal of the hydrogen ions from the system contributes to the ion gradient used in the process of chemiosmosis.

Functional role of electron transport system in metabolism

During various steps in glycolysis and the citric acid cycle, the oxidation of certain intermediate precursor molecules causes the reduction of NAD+ to NADH+ and FAD to FADH2. NADH and FADH2 then transfer protons and electrons to the electron transport chain to produce additional ATPs by oxidative phosphorylation.

b) Uncouplers or uncoupling agents are site specific inhibitors of electron transport. These compounds prevent the passage of electrons by binding to component of the chain, blocking the oxidation or reduction reactions.

Examples of uncoupling agent-

Rotenone, a plant product, that inhibits the transfer of electrons through complex 1.

Cyanide, binds with complex 4, and inhibit the terminal transfer of electrons to oxygen.

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