Cytochrome oxidase complex

Why has nature chosen this rather convoluted path for electrons in Complex 111 First of all. Complex 111 takes up two protons on the matrix side of the inner membrane and releases four protons on the cytoplasmic side for each pair of electrons that passes through the Q cycle. The apparent imbalance of two protons in ior four protons out is offset by proton translocations in Complex rV, the cytochrome oxidase complex. The other significant feature of this mechanism is that it offers a convenient way for a two-electron carrier, UQHg, to interact with the bj and bfj hemes, the Rieske protein Fe-S cluster, and cytochrome C, all of which are one-electron carriers. 

Cytochrome ala (a Cu/heme protein cytochrome oxidase, complex IV) transfers electrons to oxygen... 

Fig. 17.9 Model of the mechanism of Fe " oxidation by Thioba-cillusferrooxidans. PL-Fe phospholipid bound Fe x enzyme (unidentified) Ru rusticyane, a Cu-containing protein cyt c c-type cytochrome cyt ox cytochrome oxidase complex ATP adenosine 5 -triphosphate (Ghiorse Ehrlich, 1992 with permission).

FIGURE 19-13 Critical subunits of cytochrome oxidase (Complex IV). The bovine complex is shown here (PDB ID 10CC). (a) The core of Complex IV, with three subunits. Subunit I (yellow) has two heme groups, a and a3 (red), and a copper ion, CuB (green sphere). Heme a3 and CuB form a binuclear Fe-Cu center. Subunit II (blue) contains two Cu ions (green spheres) complexed with the —SH groups of two Cys residues in a binuclear center, CuA, that resembles the 2Fe-2S centers of iron-sulfur proteins. This binuclear center and the cytochrome... 

For reasons discussed in Chapter 20, plants must carry out this reaction even when they do not need NADH for ATP production. To regenerate NAD+ from unneeded NADH, plant mitochondria transfer electrons from NADH directly to ubiquinone and from ubiquinone directly to 02, bypassing Complexes III and IV and their proton pumps. In this process the energy in NADH is dissipated as heat, which can sometimes be of value to the plant (Box 19-1). Unlike cytochrome oxidase (Complex IV), the alternative QH2 oxidase is not inhibited by cyanide. Cyanide-resistant NADH oxidation is therefore the hallmark of this unique plant electron-transfer pathway. 

III) transfers electrons from reduced ubiquinone (UQH2) to cytochrome c. And finally, cytochrome oxidase (complex... 

There is additional evidence that the electron-transfer complexes are not connected in fixed chains. If most of the cytochrome oxidase complexes in the membrane are inhibited with CO, the few molecules that remain uninhibited are still able to catalyze oxidation of all the cytochrome c by 02. This suggests that cytochrome c can diffuse from one cytochrome oxidase complex to another, rather than remaining bound to an individual complex. Also, cytochrome c, UQ, and the complexes themselves move about at different rates, which means that they cannot all stay stuck together. 

The purification and characterization of individual cytochromes (simple or complex) and other redox centres in electron-transfer chains leads to a study of their interactions with each other, with the ultimate objective of reconstituting parts of the chain. Approaches to this problem will be illustrated724 with reference to the reaction of cytochrome c with ubiquinol cytochrome c reductase (complex III, cytochrome bcx) and cytochrome oxidase (complex IV) as shown in equation (2l). 

Step 3 Complex IV. The cytochrome oxidase complex consists of at least 13 polypeptides and functions as a dimer. It accepts electrons form cytochrome c and transfers them to the final acceptor oxygen. From two molecules of reduced cytochrome c, this reaction pumps two protons (one proton/electron) to the intermembrane space. 

ETC - cytochrome oxidase (complex III) [deadly within minutes at 300ppm] generated from Zyklon B in Second World War Holocaust mass murder of Jews in Auschwitz-Birkenau... 

Mitochondria contain ubiquinone (also known as coenzyme Q), which differs from plastoquinone A (Chapter 5, Section 5.5B) by two methoxy groups in place of the methyl groups on the ring, and 10 instead of 9 isoprene units in the side chain. A c-type cytochrome, referred to as Cyt Ci in animal mitochondria, intervenes just before Cyt c a h-type cytochrome occurring in plant mitochondria is involved with an electron transfer that bypasses cytochrome oxidase on the way to 02. The cytochrome oxidase complex contains two Cyt a plus two Cyt a3 molecules and copper on an equimolar basis with the hemes (see Fig. 5-16). Both the Fe of the heme of Cyt a3 and the Cu are involved with the reduction of O2 to H20. Cytochromes a, >, and c are in approximately equal amounts in mitochondria (the ratios vary somewhat with plant species) flavoproteins are about 4 times, ubiquinones 7 to 10 times, and pyridine nucleotides 10 to 30 times more abundant than are individual cytochromes. Likewise, in chloro-plasts the quinones and the pyridine nucleotides are much more abundant than are the cytochromes (see Table 5-3). 

Ostermeier, C., Harrenga, A., Ermler, U., and Michel, H., 1997, Structure at 2. 7 resolution of the Paracoccus denitificans two-subunit cytochrome oxidase complexed with an antibody fragment, Proc. Nad. Acad. Sci. USA 94 10547810553. 

Cytochrome c transfers electrons from cytochrome Ci, the terminal component of complex III, to the four redox centers of the cytochrome oxidase complex. The transfer of four electrons from each of the four redox centers of the cytochrome oxidase complex to an oxygen molecule... 

The property of NO of inhibiting mitochondrial electron transfer was first recognized in 1994 by two British research groups [14, 15] that reported the inhibition of brain and muscle cytochrome oxidase (complex IV) activity by low NO concentrations in a reversible and Oj-competitive manner. More related to the scope of this review is the NO inhibition of electron transfer at complex III, ubiquinol-cytochrome c reductase, the second NO-sensitive point in the respiratory chain, where inhibition of electron transfer between cytochromes b and c enhances mitochondrial H2O2 production [16]. Nitric oxide, produced by NO donors or by mitochondrial nitric oxide synthase (mtNOS), inhibits complex III electron transfer and increases Oy and H2O2 production in sub-mitochondrial particles and in mitochondria. Complex IV is more sensitive to NO inhibition (IC5o=O.l pM) than complex III (IC5o=O.2 pM). 

Cytochrome oxidase (complex IV) is a protein complex that catalyzes the 4-electron reduction of Oz to form HzO. The membrane-spanning complex (Figure 10.8) in mammals may contain between six and thirteen subunits, depending on species. It also contains two atoms of copper in addition to the heme iron atoms of cytochromes a and a3. (The copper atoms alternate between the +1 and +2 oxidation states, Cu1+ and Cu2+.) The iron atom of cyt a3 is closely associated with a copper atom referred to as CuB. The other copper atom (CuA) is a short distance from the heme of cyt a. Cytochrome c, a protein that is loosely attached to the inner membrane on its outer surface, transfers electrons one at a time to cyt a and CuA. The electrons are then donated to cyt a3 and CuB, which occur on the matrix (inner) side of the membrane. This electron shuttle allows 4 electrons and 4 protons to be delivered to the dioxygen molecule bound to cyt a3-Fe2+. Two water molecules are formed and leave the site. 

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. 

Cyanide is a respiratory inhibitor that blocks electron transfer from cytochrome oxidase (Complex IV) to oxygen in the electron transport system (Figure 15.9). 

The last cytochrome complex is cytochrome oxidase, which passes electrons from cytochrome c to O2 (see Fig. 21.5). It contains cytochromes a and a and the oxygen binding site. A whole oxygen molecule, O2, must accept four electrons to be reduced to 2 EI2O. Bound copper (Cu ) ions in the cytochrome oxidase complex facilitate the collection of the four electrons and the reduction of O2. 

Cytochrome c is only loosely attached to the inner mitochondrial membrane, and shuttles the electrons within the intermembrane space in a rotating mode from the cytochrome-bci complex to the cytochrome-oxidase complex. Repeated electron transfer cycles within the cytochrome-oxidase complex ultimately reduce oxygen to water. 

---