Electron transport cytochrome oxidase

See also Electron Transport, Cytochrome Oxidase, Inhibitors and Artificial CyOfliCl Electron Acceptors, Azide, Carbon Monoxide, Complex IV... 

Cu Laccase, oxidases Plastocyanin photosynthetic electron transport Cytochrome c oxidase mitochondrial electron transport... 

Electron transport through oxidases in the plasma membrane contributes to, or controls, part of the proton release from the cell. The details of oxidase function and the mechanism of control remain to be elucidated. The NADPH oxidase of neutrophils is a special case in which proton transport is coupled to the cytochrome >557 electron carrier. This type of proton transport has its precedents in the well-characterized proton pumping through electron carriers in mitochondrial and chloroplast membranes and prokaryotic plasma membranes. 

We already encountered the respiratory electron transfer chain in Chapter 5, and in the present context. Figure 13.8 serves as a reminder that the structures of many of the components have been determined (Hosier, Ferguson-Miller, Mills, 2006). Electrons flow from NADH/NAD" " and succinate (Complexes I and II) via Coenzyme Q to the cytochrome bc complex (Complex III) and are then transferred via cytochrome c to cytochrome c oxidase (CcO) (Complex IV). We will discuss the electron transport cytochromes in the next section. 

The answer is b. (Murray, pp 123-148. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) The entry point into the electron transport chain for electrons from FADH2 flavoproteins is ubiquinone, which is referred to as Q or QH2 in the reduced state. Ubiquinone carries these electrons to cytochrome oxidase, the next step in the respiratory chain. This... 

Cytochrome Oxidase (also known as complex IV) is an iron and copper containing enzyme in the electron transport system. It catalyzes the final step in the electron transport process - the transfer of electrons and protons to oxygen, to form water (Figures 15.2,15.3, 15.10). Transfer of electrons through cytochrome oxidase can be blocked by cyanide, azide, and carbon monoxide. 

Cyanide blocks the transfer of electrons from cytochrome oxidase to O2. Therefore, all the respiratory-chain components become reduced and electron transport ceases consequently, oxidative phosphorylation stops. An artificial electron acceptor -with an appropriate redox potential, such as methylene blue, can reoxidize some components of the respiratory chain, reestablish a proton gradient, and thereby restore ATP synthesis. The methylene blue takes the place of cytochrome oxidase as a means of transferring electrons to O2, which remains the terminal electron acceptor. 

The oxidant-generating enzyme of activated neutrophils (and other phagocytes) is a membrane-associated, electron-transporting NADPH oxidase, which consists of a flavoprotein and low-potential cytochrome, i.e., cytochrome b 245 (Segal, 1989). This oxidase is present in the latent form and is activated during exposure of the cells to a variety of diverse signals such as leukoattractants and leukotrienes (Babior, 1984 Weiss, 1989). 

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. 

Write a balanced equation for the reduction of molecular oxygen by reduced cytochrome e as carried out by complex IV (cytochrome oxidase) of the electron transport pathway. 

The electron transport chain system responsible for the respiratory burst (named NADPH oxidase) is composed of several components. One is cytochrome 6558, located in the plasma membrane it is a heterodimer, containing two polypeptides of 91 kDa and... 

P. Mitchell (Nobel Prize for Chemistry, 1978) explained these facts by his chemiosmotic theory. This theory is based on the ordering of successive oxidation processes into reaction sequences called loops. Each loop consists of two basic processes, one of which is oriented in the direction away from the matrix surface of the internal membrane into the intracristal space and connected with the transfer of electrons together with protons. The second process is oriented in the opposite direction and is connected with the transfer of electrons alone. Figure 6.27 depicts the first Mitchell loop, whose first step involves reduction of NAD+ (the oxidized form of nicotinamide adenosine dinucleotide) by the carbonaceous substrate, SH2. In this process, two electrons and two protons are transferred from the matrix space. The protons are accumulated in the intracristal space, while electrons are transferred in the opposite direction by the reduction of the oxidized form of the Fe-S protein. This reduces a further component of the electron transport chain on the matrix side of the membrane and the process is repeated. The final process is the reduction of molecular oxygen with the reduced form of cytochrome oxidase. It would appear that this reaction sequence includes not only loops but also a proton pump, i.e. an enzymatic system that can employ the energy of the redox step in the electron transfer chain for translocation of protons from the matrix space into the intracristal space. 

Hydrogen sulfide inhibits mitochondrial cytochrome oxidase, resulting in disruption of the electron transport chain and impairing oxidative metabolism. Nervous and cardiac tissues, which have the highest oxygen demand (e.g., brain and heart), are especially sensitive to disruption of oxidative metabolism (Ammann 1986 Hall 1996). 

Oxidation is intimately linked to the activation of polycyclic aromatic hydrocarbons (PAH) to carcinogens (1-3). Oxidation of PAH in animals and man is enzyme-catalyzed and is a response to the introduction of foreign compounds into the cellular environment. The most intensively studied enzyme of PAH oxidation is cytochrome P-450, which is a mixed-function oxidase that receives its electrons from NADPH via a one or two component electron transport chain (10. Some forms of this enzyme play a major role in systemic metabolism of PAH (4 ). However, there are numerous examples of carcinogens that require metabolic activation, including PAH, that induce cancer in tissues with low mixed-function oxidase activity ( 5). In order to comprehensively evaluate the metabolic activation of PAH, one must consider all cellular pathways for their oxidative activation. 

Abnormalities of the respiratoiy chain. These are increasingly identified as the hallmark of mitochondrial diseases or mitochondrial encephalomyopathies [13]. They can be identified on the basis of polarographic studies showing differential impairment in the ability of isolated intact mitochondria to use different substrates. For example, defective respiration with NAD-dependent substrates, such as pyruvate and malate, but normal respiration with FAD-dependent substrates, such as succinate, suggests an isolated defect of complex I (Fig. 42-3). However, defective respiration with both types of substrates in the presence of normal cytochrome c oxidase activity, also termed complex IV, localizes the lesions to complex III (Fig. 42-3). Because frozen muscle is much more commonly available than fresh tissue, electron transport is usually measured through discrete portions of the respiratory chain. Thus, isolated defects of NADH-cytochrome c reductase, or NADH-coenzyme Q (CoQ) reductase suggest a problem within complex I, while a simultaneous defect of NADH and succinate-cytochrome c reductase activities points to a biochemical error in complex III (Fig. 42-3). Isolated defects of complex III can be confirmed by measuring reduced CoQ-cytochrome c reductase activity. 

HCN is a systemic poison toxicity is due to inhibition of cytochrome oxidase, which prevents cellular utilization of oxygen. Inhibition of the terminal step of electron transport in cells of the brain results in loss of consciousness, respiratory arrest, and ultimately, death. Stimulation of the chemoreceptors of the carotid and aortic bodies produces a brief period of hyperpnea cardiac irregularities may also occur. The biochemical mechanisms of cyanide action are the same for all mammalian species. HCN is metabolized by the enzyme rhodanese which catalyzes the transfer of sulfur from thiosulfate to cyanide to yield the relatively nontoxic thiocyanate. 

---