Cytochrome electron transport pathway

FIGURE 21.21 A model for the electron transport pathway in the mitochondrial inner membrane. UQ/UQH9 and cytochrome e are mobile electron carriers and function by transferring electrons between the complexes. The proton transport driven by Complexes I, III, and IV is indicated. 

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. 

Figure 14.1. Proposed electron-transport pathway in the acetogenic bacteria M. thermoacetica and M. thermoautotrophica. Cyt., cytochrome MTi/FD//, methylene tetrahydrofolate dehydrogenase Fd, ferredoxin Fp, flavoprotein H2ase, hydrogenase.

When little NADP+ is available to accept electrons, an alternative electron transport pathway is used. The high-energy electron donated by photosystem I passes to ferredoxin, then the cytochrome bf complex, then plastocyanin and back to the P700 of photosystem I. The resulting proton gradient generated by the cytochrome bf complex drives ATP synthesis (cyclic photophosphorylation) but no NADPH is made and no 02 is produced. 

Several inherited disorders are associated with faulty operation of the electron transport pathway. ATP production is diminished in such cases. These disorders are known as mitochondrial myopathies, and they are associated with the absence of specific polypeptide chains found in complexes I, III, or IV. In many cases, the problem may be traced to specific lesions in mitochondrial DNA, which codes for at least 13 polypeptide chains found in these complexes. Myopathies are tissue specific some affect the heart, others the skeletal muscle. Many are accompanied by lactic acidosis, because the inability to reduce NADH normally results in its accumulation and the channeling of pyruvate toward lactic acid production. In complex I disorders, the oxidation of FADH2 is not impeded. In complex III lesions, neither NADH nor FADH2 can be oxidized. However, use has been made by B. Chance and colleagues of menadione (Chapter 6) and ascorbic acid in such cases. The former can oxidize UQH2, whereas ascorbate can oxidize menadione and reduce cytochrome c. Marked clinical improvement in affected patients follows such treatment. 

The system depends on an electron transport pathway that transfers electrons from NADPH through a flavoprotein (NADPH cytochrome P-450 reductase) to cytochrome P-450 that is the terminal oxidase of the chain (10). The xenobiotic first forms a complex with the oxidized form o cytochrome P-450 which is reduced by an electron passing down the chain from NADPH. The reduced cytochrome P-450/substrate complex then reacts with and activates molecular oxygen to an electrophilic oxene species (an electron deficient species similar to singlet oxygen) that is transferred to the substrate with the concommitant formation of water. Cytochrome P-450 thus acts primarily as an oxene transferase (2). Substrate binding is a relatively nonspecific, passive process that serves to bring the xenobiotic into close association with the active center and provide the opportunity for the oxene transfer to occur. 

The proteins of the respiratory chain are NADH dehydrogenase, cytochrome b, cytochrome Cj, cytochrome c, cytochrome aj, and cytochrome a. Cytochromes ai and as form a complex known as cytochrome c oxidase. The proteins are listed in the order in which they are used in the electron transport pathway. The proteins are all membrane-bound proteins, though cytochrome c is only weakly bound to the outer surface of the irmer membrane. Its polypeptide chain is not inserted in the membrane. Electrons are delivered in pairs, via NAD, to-the respiratory chain. It is thought that three protons are driven out of the mitochondrion for each pair of electrons from NAD passing down the respiratory chain and through cytochrome oxidase to oxygen (Cross, 1981 Hatefi, 1985). Further details are given in Chapter 5 and xmder Iron in Chapter 10. 

Cytochrome b /also serves as an intermediate in a non-linear, or so-called cyclic, electron-transport pathway around PS I, as formulated in Fig. 1 (B). A third function of Cyt b /is translocation of protons across the thylakoid membrane during electron transfer from plastoquinol to plastocyanin [Fig. 1 (C)]. The unique effects resulting from electron transport and proton translocation in the cytochrome b(f complex are the production of an electrochemical potential and a pH gradient across the thylakoid membrane to provide energy in a form needed for ATP synthesis (see the following chapter). 

Recall that during mitochondrial electron transport, H20 is formed as a consequence of the sequential transfer of 4 electrons to 02. During this process, several ROS are formed. Cytochrome oxidase (and other oxygen-activating proteins) traps these reactive intermediates within its active site until all 4 electrons have been transferred to oxygen. However, electrons may leak out of the electron transport pathway and react with 02 to form ROS (Figure 10.18). 

As mentioned (see p. 320), ROS are generated during several other cellular activities besides the reduction of Oz to form H20. These include the biotransformation of xenobiotics and the respiratory burst (Figure 10.20) in white blood cells. In addition, electrons often leak from the electron transport pathways in the endoplasmic reticulum (e.g., the cytochrome P450 electron transport system) to form superoxide by combining with Oz. 

Vasil ev S, Brudwig GW, Bruce D. The X-ray structure of photosystem II reveals a novel electron transport pathway between P680, cytochrome b559 and the energy-quenching cation, Chlz. FEBS Lett 2003 543 159-163. 

The discoveries of the structures of EMN and FAD as well as NAD during the 1930s provided insights into coenzymes associated with dehydrogenases, such as succinate dehydrogenase (FAD) and malate dehydrogenase (NAD ). By 1939, studies in many laboratories led to consensus for an electron-transport pathway involving four distinct cytochrome (cyt) species ... 

Irrespective of composition, the electron transport pathway is thought to involve the following sequence NADPH -> FAD cyt b O2, in which the FAD is properly situated to mediate the two-to-one noncomplementary transfer of electrons from NADPH to the cytochrome. An FAD binding protein with the appropriate reduction potential has been identified in neutrophils by ESR spectroscopy. The general features for activation of the neutrophil respiratory oxidase are summarized schematically in Figure 3. 

Since develops under both MV-mediated and PMS-mediated electron transport, q appears to be a PSI activity which is expressed as PSIl fluorescence quenching. Oxborough and Horton (3) have suggested the antimy-cin target site could be a cyclic electron-transport component that Is independent of the linear electron-transport pathway. Cytochromes... 

Chun YJ, Shimada T, Sanchez-Ponce R, Martin MV, Lei L, Zhao B, Kelly SL, Waterman MR, Lamb DC, Guengerich FP (2007) Electron transport pathway for a Streptomyces cytochrome P450. J Biol Chem 282 17486-17500... 

F.P. (2007) Electron transport pathway for a Streptomyces cytochrome P450 cytochrome P450 105 D5-catalyzed fatty acid hydroxylation in Streptomyces coelicolor A3(2). J. Biol. Chem., 282 (24), 17486-17500. 

Synthesis of both progesterone and 17a-hydroxyprogesterone occurs in the endoplasmic reticulum from which these intermediates migrate to the mitochondrion, the location of the first reaction and the remainder of the pathways. The monooxygenases involved are all cytochrome P-450 enzymes but different electron-transport pathways transfer the electrons from NADPH to the... 

In the third complex of the electron transport chain, reduced coenzyme Q (UQHg) passes its electrons to cytochrome c via a unique redox pathway known as the Q cycle. UQ cytochrome c reductase (UQ-cyt c reductase), as this complex is known, involves three different cytochromes and an Fe-S protein. In the cytochromes of these and similar complexes, the iron atom at the center of the porphyrin ring cycles between the reduced Fe (ferrous) and oxidized Fe (ferric) states. 

Studies (see, e.g., (101)) indicate that photosynthesis originated after the development of respiratory electron transfer pathways (99, 143). The photosynthetic reaction center, in this scenario, would have been created in order to enhance the efficiency of the already existing electron transport chains, that is, by adding a light-driven cycle around the cytochrome be complex. The Rieske protein as the key subunit in cytochrome be complexes would in this picture have contributed the first iron-sulfur center involved in photosynthetic mechanisms (since on the basis of the present data, it seems likely to us that the first photosynthetic RC resembled RCII, i.e., was devoid of iron—sulfur clusters). 

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. 

Figure 5.8. Proposed scheme of electron transport in neutrophils. In this scheme, electrons are transferred from NADPH — FAD—> cytochrome b —> 02. The values shown in the boxes are the redox midpoint potentials for each of the constituents of the pathway. NADPH donates two electrons upon oxidation, but single electrons are transferred from the flavin to the cytochrome b via the formation of FADH-. Source Redrawn from Cross and Jones (1991).

Reviewing the criteria for inclusion of components into the electron transport chain, Slater (1958) highlighted considerations previously advanced by H.A. Krebs as necessary to establish a pathway, namely that the amounts of enzyme present must be commensurate with enzymic activity in the preparation, activity should be fully restored by the reintroduction of the postulated component into an inhibited or depleted preparation, and that the rates of oxidation and reduction of components must be at least as great as those in the system overall. Reduction of cytochrome b by the systems then in use was thought by Chance (1952) and Slater (1958) to be too slow for the inclusion of this cytochrome into the main chain. 

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