Electron transport chain cytochrome oxidase, complex

Cytochrome c, like UQ is a mobile electron carrier. It associates loosely with the inner mitochondrial membrane (in the intermembrane space on the cytosolic side of the inner membrane) to acquire electrons from the Fe-S-cyt C aggregate of Complex 111, and then it migrates along the membrane surface in the reduced state, carrying electrons to cytochrome c oxidase, the fourth complex of the electron transport chain. 

The electron transport chain is vital to aerobic organisms. Interference with its action may be life threatening. Thus, cyanide and carbon monoxide bind to haem groups and inhibit the action of the enzyme cytochrome c oxidase, a protein complex that is effectively responsible for the terminal part of the electron transport sequence and the reduction of oxygen to water. 

Oxidizible substrates from glycolysis, fatty acid or protein catabolism enter the mitochondrion in the form of acetyl-CoA, or as other intermediaries of the Krebs cycle, which resides within the mitochondrial matrix. Reducing equivalents in the form of NADH and FADH pass electrons to complex I (NADH-ubiquinone oxidore-ductase) or complex II (succinate dehydrogenase) of the electron transport chain, respectively. Electrons pass from complex I and II to complex III (ubiquinol-cyto-chrome c oxidoreductase) and then to complex IV (cytochrome c oxidase) which accumulates four electrons and then tetravalently reduces O2 to water. Protons are pumped into the inner membrane space at complexes I, II and IV and then diffuse down their concentration gradient through complex V (FoFi-ATPase), where their potential energy is captured in the form of ATP. In this way, ATP formation is coupled to electron transport and the formation of water, a process termed oxidative phosphorylation (OXPHOS). 

In juvenile liver fluke and miracidia, a respiratory chain up to cytochrome c oxidase is active and all evidence obtained so far indicates that in F. hepatica at least this electron-transport chain is not different from the classical one present in mammalian mitochondria (Figs 20.1 and 20.2). In the aerobically functioning stages, electrons are transferred from NADH and succinate to ubiquinone via complex I and II of the respiratory chain, respectively. Subsequently, these electrons are transferred from the formed ubiquinol to oxygen via the complexes III and IV of the respiratory chain. 

The principal function of cyt. c is to form complexes through a defined interface with protein partners in our cells. This is most established for eukaryotic cytochrome c within the mitochondrial electron transport chain (ETC), a process required for carrying out the oxidative phosphorylation of ATP.4 Formation of a complex with cyt. c reductase (an electron-donor protein from complex III) and cyt. c oxidase (an electron-acceptor protein from complex IV) leads to the transfer of electrons between otherwise separated proteins. More recently cyt. c has been found to play a critical role in the process of apoptosis or programmed cell death This in turn has led to a resurgence of interest in all aspects of cyt. c research.5 Again protein-protein interactions have been shown be essential with mitochrondrial cyt. c binding to such proteins as APAF-1 to form the multi-protein species known as the apoptosome that is now thought to be a requirement for apoptosis.6,7... 

The main part of the electron transport chain consists of three large protein complexes embedded in the inner mitochondrial membrane, called NADH dehydrogenase, the cytochrome bcx complex and cytochrome oxidase. Electrons flow from NADH to oxygen through these three complexes as shown in Fig. 1. Each complex contains several electron carriers (see below) that work sequentially to carry electrons down the chain. Two small electron carriers are also needed to link these large complexes ubiquinone, which is also called coenzyme Q (abbreviated here as CoQ), and cytochrome c (Fig. 1). 

Accompanying electron flow in mitochondria, H+ is transported from the matrix side of the inner membrane to the lumen between the limiting membranes, i.e., within the cristae (Figs. 1-9 and 6-9). Certain electron flow components are situated in the membranes such that they can carry out this vectorial movement. Protein Complex I, which oxidizes NADH, apparently transfers four H+ s across the inner membrane per pair of electrons from NADH. Complex II, which oxidizes FADH2 and leads to the reduction of a ubiquinone whose two electrons move to Complex III, apparently causes no H+ s to move from the matrix to the lumen. Transport of four H+ s from the matrix to the lumen side most likely occurs through protein Complex III per pair of electrons traversing the electron transport chain. Complex IV (cytochrome oxidase) may also transport four H+ s (Fig. 6-9 summarizes these possibilities). We also note that two H+ s are necessary for the reduction of 02 to H20, and these protons can also be taken up on the matrix side (Fig. 6-9). 

Figure 7.27 The electron transport chain showing the three phosphorylation sites and points where insecticides inhibit this process. Flavoprotein represents complex I (NADH dehydrogenase). Coenzyme Q also accepts electrons from succinate dehydrogenase (complex II). Cytochrome b represents complex III consisting of cytochrome bc complex. Cytochrome oxidase represents complex IV.

The inner membrane of mitochondria is the site of respiratory electron transport and within the inner membrane and the intermembrane space (IMS) of mitochondria are two important copper containing enzymes. First, cytochrome c oxidase (COX) represents the terminal electron acceptor in the respiratory chain and two subunits of this large complex enzyme contain copper sites. A second enzyme in the mitochondria that requires copper is SODl, as described above. Although the vast majority of SODl is cytosolic, a small fraction of this enzyme enters the IMS of the mitochondria where it is believed to directly scavenge superoxide anions produced as a by-product of the electron transport chain. 

The components of the electron transport chain have various cofactors. Complex I, NADH dehydrogenase, contains a flavin cofactor and iron sulfur centers, whereas complex ID, cytochrome reductase, contains cytochromes b and Cj. Complex IV, cytochrome oxidase, which transfers electrons to oxygen, contains copper ions as well as cytochromes a and a. The general structure of the cytochrome cofactors is shown in Figure 16-2. Each of the cytochromes has a heme cofactor but they vary slightly. The b-type cytochromes have protoporphyrin IX, which is identical to the heme in hemoglobin. The c-type cytochromes are covalently bound to cysteine residue 10 in the protein. The a-type... 

In metazoans, the electron transport chain consists of four integral membrane complexes localized to the inner mitochondrial membrane complex I (NADH-ubiquinone oxidoreductase), complex II (succinate-ubiquinone oxidoreductase), complex III (ubiquinol-cytochrome c oxidoreductase) and complex IV (cytochrome c oxidase), plus coenzyme Q (ubiquinone) and cytochrome c. As first shown by Fry and Beesley (1991), the plasmodial electron transport chain differs from the metazoan system in lacking complex I however, a single subunit NADH dehydrogenase is present and is homologous to that found in plants, bacteria and yeast but not in animals (Krungkrai, 2004 Vaidya, 2004,2005 van Dooren et al., 2006). 

Other cellular targets of CO include cytochrome oxidase (Complex IV) of the mitochondrial electron transport chain, resulting in the failure of the oxidative phosphorylation pathway to reduce oxygen to water and provide ATP, the chemical energy for fhe cells of the body. 

Deficiencies of electron transport In cells, complete transfer of electrons from NADH and FAD(2H) through the chain to O2 is necessary for ATP generation. Impaired transfer through any complex can have pathologic consequences. Fatigue can result from iron-defeciency anemia, which decreases Fe for Fe-S centers and cytochromes Cytochrome Cj oxidase, which contains the O2 binding site, is inhibited by cyanide Mitochondrial DNA (mtDNA), which is maternally inherited, encodes some of the subunits of the electron transport chain complexes and ATP synthase. Oxphos diseases are caused by mutations in nuclear DNA or mtDNA that decrease mitochondrial capacity for oxidative phosphorylation. 

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