ELECTRON TRANSPORT CHAIN OVERVIEW OF THE ELECTRON TRANSPORT CHAIN Q-CYCLE
The Q-cycle is initiated when CoQH2 diffuses through the bilipid layer to the CoQH2 binding site which is near the intermembrane face. This CoQH2 binding site is called the QP site. The electron transfer occurs in two steps. First one electron from CoQH2 is transferred to the Rieske protein (a Fe-S protein) which transfers the electron to cytochrome c1. This process releases 2 protons to the intermembrane space.
(a) First half of Q cycle
Coenzyme Q is now in a semiquinone anionic state, CoQHx - still bound to the QP site. The second electron is transferred to the bL heme which converts CoQHx - to CoQ. This reoxidized CoQ can now diffuse away from the QP binding site. The bL heme is near the P-face. The bL heme transfers its electron to the bH heme which is near the N-face. This electron is then transferred to second molecule of CoQ bound at a second CoQ binding site which is near the N-face and is called the QN binding site. This electron transfer generates a CoQx - radical which remains firmly bound to the QN binding site. This completes the first half of the Q cycle.
(b) Second half of Q cycle
The second half of the Q-cycle is similar to the first half. A second molecule of CoQH2 binds to the QP site. In the next step, one electron from CoQH2 (bound at QP) is transferred to the Rieske protein which transfers it to cytochrome c1. This process releases another 2 protons to the intermembrane space. The second electron is transferred to the bL heme to generate a second molecule of reoxidized CoQ. The bL heme transfers its electron to the bH heme. This electron is then transferred to the CoQ-radical still firmly bound to the QN binding site. The take up of two protons from the N-face produces CoQH2 which diffuses from the QN binding site. This completes Q cycle.
The net result of the Q-cycle is 2e- transported to cytochrome c1. Two protons were picked up from the N-face in the second half of the Q-cycle and 4 protons total were released into the intermembrane space. The two electron carrier CoQH2 gives up its electrons one at a time to the Rieske protein and the bL heme both of which are one electron carriers.
The electrons that end up on cytochrome c1 are transferred to cytochrome c. Cytochrome c is the only water soluble cytochrome. Cytochrome c is coordinated to ligands that protect the iron contained in the heme from oxygen and other oxidizing agents. Cytochrome c is a mobile electron carrier that diffuses through the intermembrane space shuttling electrons from the c1 heme of complex III to CuA site of complex IV.
Cytochrome c shown to the left. The heme is linked to the protein by 4 cysteine linkages shown in yellow. A methionine sulfur atom is coordinated to the iron compexed in the heme. A histidine residue protects the iron from oxygen and other potential ligands.
15.3.5. Complex IV
The cytochrome oxidase complex also functions as a dimer. Each monomer contains 13 different polypeptide chains, including two cytochromes and two copper atoms. The complex accepts one electron at a time from cytochrome c and passes them to oxygen. The oxidation state of Fe+2 is converted to Fe+3 upon the addition of electron.
Oxygen has a high affinity for electrons so it releases a large amount of free energy when it is reduced to form water. This is the evolution of cellular respiration and which enabled organisms to harness much more energy compared to anaerobic respiration.
The cell is able to use O2 for respiration because of the cytochrome oxidase which holds oxygen between a heme-linked iron atom and a copper atom until it gets all its four electrons and released as 2H2O.
Cytochrome c oxidase contains 2 heme centers, cytochrome a and cytochrome a3 and two copper proteins. The copper sites are called CuA and CuB. CuA is associated with cytochrome a and CuB is associated with cytochrome a3 .
The copper sites function as one electron carriers cycling between the cuprous state Cu+ and the cupric state Cu2+ Just like iron sulphur proteins. Cytochrome a transfers one electron to CuB.
A second cytochrome c binds and transfer its electron to CuA. CuA subsequently transferred its electron to cytochrome a which in turn is transferred to cytochrome a3. Cytochrome c is bound on the P-face of the Inner mitochondrial membrane and transfers its electron to CuA. The oxidized cytochrome c get dissociates from complex 4. CuA then transfers the electron to cytochrome a. Cytochrome a transfers the electron to CuB. A second cytochrome c binds and transfer its electron to CuA which is subsequently transferred to cytochrome a which in turn is transferred to cytochrome a3. The binuclear metal center now has two electrons bound allowing the binding of O2 to binuclear center. The next step involves the uptake of two protons and the transfer of yet another electron through the same pathway which leads to cleavage of the O-O bond and the generation of a Fe4+ metal center. The fourth electron is transferred to form a hydroxide at the heme center which becomes protonated and dissociates as H2O. The mechanism is shown below. The reduction of oxygen by complex IV involves the transfer of four electrons. Four protons are abstracted from the matrix and two protons are released into the intermembrane space. The reduction of oxygen by complex IV involves the transfer of four electrons. Four protons are abstracted from the matrix and two protons are released into the intermembrane space.
15.3.6. The mitochondrial electron-transport chain-
The standard reduction potentials of its most mobile components are indicated, as are the points where sufficient free energy is harvested to synthesize ATP and the sites of action of several respiratory inhibitors. The Complexes I, III, and IV do not directly synthesize ATP but, rather, sequester the free energy necessary to do so by pumping protons outside the mitochondrion to form a proton gradient.
15.4. Inhibitor of ETC
There are many inhibitor molecules which reveals the working of electron-transport chain. Following are some compounds –
Effect of inhibitors on electron transport. This diagram shows an idealized oxygen electrode trace of a mitochondrial suspension containing excess ADP and Pi. At the numbered points, the indicated reagents are injected into the sample chamber and the resulting changes in [O2] are recorded.
In ETS system, as we added -hydroxy-butyrate, NAD+ linked oxidation commences as -hydroxy butyrate is the source of ketone bodies. During starvation, its production increases.
As we add rotenone or amytal it interfere on inhibit NAD+ linked oxidation as it inhibit the transfer of electrons from iron-sulphur enters in complex 1 to ubiquinone. As cellular oxygen gets reduced so it creates ROS (relative oxygen species which can damage DNA and components of mitochondria).
In ETS system as succinate is added so it is generated in mitochondria by tricarboxylic acid cycle (TCA), succinate can exit the mitochondrial matrix only functional in cytoplasm as well as extra cellular space changing gene expression.
As succinate added, FAD linked glycosylation begins but antimycin is added it inhibits FAD-linked oxidation.
Cyanide is an inhibitor of enzyme cytochrome oxidase in the IV complex of ETS; as it prevent O2 from binding. As of now, O2 cannot bind nor can reduced to water. Because of this, mitochondria can't make ATP.
- Book COVER AND ABOUT US
- CHEMICAL BONDING
- AMINO ACIDS
- PROTEIN STRUCTURE
- RAMACHANDRAN PLOT
- PROTEIN STABILITY
- KINETIC ANALYSIS
- REGULATION OF GLYCOLYSIS
- TRICARBOXYLIC ACID CYCLE (TCA CYCLE)
- REGULATION OF THE CITRIC ACID CYCLE
- GLYOXYLATE CYCLE OR KREBS KORNBERG CYCLE
- ELECTRON-TRANSPORT CHAIN
- MECHANISMS OF OXIDATIVE PHOSPHORYLATION
- PENTOSE PHOSPHATE PATHWAY
- LIPID METABOLISM
- FATTY ACID OXIDATION
- DNA STRUCTURE
- NUCLEOTIDE BIOSYNTHESIS