electrontransportchain fully explained-.pptx

Elecron Transport Chain fully detailed notes

1. Objectives: By the end of this lecture students will be well aware of the following concepts: Oxidative phosphorylation used to form ATP. Protein complexes ( labeled complex I-IV) in the electron transport chain, which are involved in moving electrons from NADH and FADH 2  to molecular oxygen. Key terminologies used Mechanism of electron transport chain

2. Introduction: The electron transport chain (ETC) is the major consumer of O2 in mammalian cells. The ETC passes electrons from NADH and FADH2 to protein complexes and mobile electron carriers.  Coenzyme Q ( CoQ ) and cytochrome c ( Cyt c) are mobile electron carriers in the ETC, and O2 is the final electron recipient. The malate and glycerol 3-P shuttles regenerate cytoplasmic NAD+ for glycolysis, and deliver reducing equivalents to the mitochondrial ETC.

3. Cont.. In non-biologic systems, energy is produced in the form of heat by direct reaction between hydrogen and oxygen, then heat can be transformed into mechanical or electric energy. This process is explosive, inefficient and uncontrolled. In biologic systems, the cells use electron transport chain to transfer electrons stepwise from substrates to oxygen. Thus producing energy gradually to prevent sudden release of huge amount of energy, which may be wasted or destructive to the cells. This process is stepwise, efficient and controlled.

4. Key terms: prosthetic group : The non-protein component of a conjugated protein. complex : A structure consisting of a central atom, molecule, or protein weakly connected to surrounding atoms, molecules, or proteins. ubiquinone : A lipid soluble substance that is a component of the electron transport chain and accepts electrons from complexes I and II. Oxidative phosphorylation is a highly efficient method of producing large amounts of ATP, the basic unit of energy for metabolic processes. During this process electrons are exchanged between molecules, which creates a chemical gradient that allows for the production of ATP. The most vital part of this process is the electron transport chain, which produces more ATP than any other part of cellular respiration.

5. Cont.. Electron transport chain is a chain of catalysts of increasing redox potential. It collects reducing equivalents (hydrogen atoms and electrons) from substrates transferring it stepwise to be oxidized in a final reaction with oxygen to form water and energy. It is also known as redox chain or respiratory chain. It is simply a chain of hydrogen and electron carriers of increasing redox potential. The electron carriers are found within four membrane-bound enzyme-complexes, which are imbedded in the inner mitochondrial membrane. Components of the electron transport chain The electron transport chain is formed of: Hydrogen and electron carriers Four membrane-bound enzyme complexes

6. Hydrogen and electron carriers of the electron transport chain 1- NAD + It is a coenzyme that acts as a hydride carrier as it carries hydride ion (H - ). It receives two hydrogen atoms (2H) from substrates as isocitrate , malate,  - hydroxy acyl CoA and  - hydroxy butyrate. Its reduced form (NADH+H + ) passes its hydrogen to flavoprotein containing FMN ( flavin mononucleotide ) and iron sulfur protein ( FeS ).

7. Cont.. 2. Flavoproteins FAD ( flavin adenine dinucleotide ) and FMN serve as hydrogen carriers, which are tightly bound to flavoproteins as a manner that prevents its reduced form from reacting with oxygen directly. There are many types of flavoproteins that have a role in electron transport chain Flavoprotein Fp 1 containing FMN ( flavin mononucleotide ) receives two hydrogen atoms from reduced NAD + passing them to coenzyme Q. Flavoproteins Fp 2 containing FAD receive two hydrogen atoms from substrates as succinate, acyl CoA and choline passing them to coenzyme Q. 3. Ubiquinone (Coenzyme Q) Ubiquinones are a group of compounds containing Quinone ring but vary according to number of isoprene units at the side chain. The most common ubiquinone is coenzyme Q that has structural similarity to vitamin K. It is a small molecule, which is soluble in lipid, so it is freely mobile in the inner mitochondrial membrane colleting reducing equivalents from the more fixed component of the respiratory chain.

8. Cont.. Ubiquinone can carry two hydrogen atoms forming ubiquinol (reduced coenzyme Q) or one hydrogen atom forming semiquinone . So, It forms a bridge between flavoproteins , which can carry 2 hydrogen atoms, and cytochrome b, which can carry one electron only. Reduced coenzyme Q passes the electrons to cytochrome b and releases 2H + into the mitochondrial matrix The oxidation of ubiquinol involves the successive action of 2 enzymes: - Ubiquinol (coenzyme Q) dehydrogenase which transfers electrons to cytochrome c. It needs cyt b, FeS protein and cyt c1 as coenzymes. - Cytochrome oxidase which transfers electrons from cyt c to oxygen. It needs cyt a and cyt a3 as coenzymes.

9. Cont.. 4- Cytochromes They are electron carriers transferring electrons from coenzyme Q to oxygen. They have given letter designation a, b and c according to their order of discovery. All cytochromes are haemoproteins but they differ in redox potential. The haeme in cytochromes differs from that of haemoglobin as the iron atom oscillates between oxidation (Fe +3 ; ferric state) and reduction (Fe +2 ; ferrous state) during the physiological action of cytochromes, while the iron of haemoglobin remains in the reduced form during its physiological action. Cytochrome c is a water soluble, peripheral membrane protein. It is relatively mobile. It is associated with iron sulfur protein in addition to the haeme group. Cytochrome a3 contains copper in addition to the haeme group. N.B. The mobile components of the electron transport chain include coenzyme Q and cytochrome c. They collect reducing equivalents from the other fixed components.

10. 5. Iron sulfur protein It is an additional component found in the electron transport chain. It is also called FeS or none- haeme iron. It consists of a cluster of cysteine residues which complex iron through covalent bonds with the sulfur of cysteine. It is associated with the flavoproteins and cytochrome b. The sulfur and iron are thought to take part in the oxidation-reduction mechanism between flavoproteins and coenzyme Q as the iron atom in these complexes oscillates between oxidation and reduction that allows them to either give up or accept electrons.

11. Enzyme Complexes of the Electron Transport Chain The enzymes of the electron transport chain are organized in the inner mitochondrial membrane in the form of four enzyme complexes. The four enzyme complexes of the electron transport chain are: Complex I : NADH dehydrogenase (NADH-ubiquinone oxidoreductase ) It is a flavoprotein that contains FMN as well as FeS protein as coenzymes It transfers hydrogen atoms from NADH+H + to ubiquinone. Complex II: Succinate dehydrogenase (succinate-ubiquinone oxidoreductase ). It is a flavoprotein that contains FAD as well as FeS protein as coenzymes It transfers hydrogen atoms from succinate to ubiquinone Complex III: Ubiquinol dehydrogenase ( ubiquinol -cytochrome c oxidoreductase ). It transfers electrons from ubiquinol to cytochrome c using cyt b and cyt c1 as coenzymes Complex IV: Cytochrome oxidase (cytochrome-oxygen oxidoreductase ) It transfers electrons from cytochrome c to oxygen. It needs cyt a and cyt a3 as coenzymes.

12. Complex I To start, two electrons are carried to the first complex aboard NADH. Complex I is composed of flavin mononucleotide (FMN) and an enzyme containing iron- sulfur (Fe-S). FMN, which is derived from vitamin B 2  (also called riboflavin), is one of several prosthetic groups or co-factors in the electron transport chain. A prosthetic group is a non-protein molecule required for the activity of a protein. Prosthetic groups can be organic or inorganic and are non-peptide molecules bound to a protein that facilitate its function. Prosthetic groups include co-enzymes, which are the prosthetic groups of enzymes. The enzyme in complex I is NADH dehydrogenase, 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; it is in this way that the hydrogen ion gradient is established and maintained between the two compartments separated by the inner mitochondrial membrane.

13. Q and Complex II Complex II directly receives FADH 2 , 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 to QH 2 , 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 FADH 2  from complex II, including succinate dehydrogenase. This enzyme and FADH 2  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 FADH 2  electrons. The number of ATP molecules ultimately obtained is directly proportional to the number of protons pumped across the inner mitochondrial membrane.

14. Complex III The third 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 heme group. 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 2+  (reduced) and Fe 3+  (oxidized). The heme molecules in the cytochromes have slightly different characteristics due to the effects of the different proteins binding them, which makes each complex. Complex III pumps protons through the membrane and passes its electrons to cytochrome c for transport to the fourth complex of proteins and enzymes. Cytochrome c is the acceptor of electrons from Q; however, whereas Q carries pairs of electrons, cytochrome c can accept only one at a time.

15. Complex IV The fourth complex is composed of cytochrome proteins c, a, and a 3 . This complex contains two heme groups (one in each of the cytochromes a and a 3 ) and three copper ions (a pair of Cu A  and one Cu B  in cytochrome a 3 ). 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 produce water (H 2 O). The removal of the hydrogen ions from the system also contributes to the ion gradient used in the process of chemiosmosis.

16. In addition to these four enzyme complexes, their is a fifth complex (complex V) which is the ATP synthase that is responsible for biosynthesis of ATP from ADP and inorganic phosphate.

17. Sequence of events in the electron transport chain The following diagram shows the sequence of events that occurs in the electron transport chain The hydrogen atoms produced from oxidation of substrates can enter the chain through FAD or NAD + . The hydrogen atoms are then successively transferred through the respiratory chain to oxygen to produce water and energy. NAD+ collects the reducing equivalents from substrates as isocitrate , malate,  - hydroxy acyl CoA and  - hydroxy butyrate, while FAD collects the reducing equivalents from substrates as succinate, acyl CoA and choline. The initial oxidation of NADH+H + is catalyzed by a membrane bound NADH dehydrogenase (complex I). The electrons are then passed to coenzyme Q.

18. Electrons from FADH2 are passed to coenzyme Q by enzyme complex II. Ubiquinol (reduced coenzyme Q) is oxidized by ubiquinol dehydrogenase (Complex III). The 2 hydrogen atoms are removed from ubiquinol but they cannot be transferred to cytochrome b as cytochromes can accept or transfer only electrons. So at this step the two hydrogen atoms liberated from coenzyme Q will be ionized giving 2 hydrogen ions and 2 electrons. The hydrogen ions will be liberated into the mitochondrial matrix and the 2 electrons will then reduce the iron in cyt b. The electrons will be successively transferred to cyt c1, cyt c, cyt a and cyt a3 Lastly, electrons are transferred to oxygen by cytochrome oxidase and ionic oxygen (O -- ) will be produced. Being negatively charged, ionic oxygen attracts 2 hydrogen ions from the mitochondrial matrix to form water .

19. Electronegativity An important feature of the electron transport chain is that the electron carriers are organized in terms of  electronegativity.  Electronegativity  is “the tendency to acquire electrons.” As you move along the electron transport chain, each electron carrier has a greater electronegativity than the one before it.    You can see this in the diagram to the left. Inside Complex I you can see the electron carriers FMN and FE . S, which are positioned next to “Q.”  “Q” can pull electrons from FE . S (because “Q” has greater electronegativity).FE . S can, in turn, pull electrons from FMN. You can imagine electrons falling “down” an energy gradient. As they fall, they release energy that can be harvested to do work.