Respiratory Cytochrome

Active fish have a better developed capillary system in the red muscle to supply oxygen to the mitochondria, and a higher haematocrit (Blaxter et al., 1971). The red muscle tissue also contains more cytochromes (respiratory proteins), and exhibits more cytochrome oxidase activity, which is responsible for transferring electrons in die respiratory chain, more efficient respiration control (oxidative phosphorylation and P/O coefficient) and a greater Atkinson charge, which characterizes energy reserve accumulated in adenyl nucleotides ... 

The branch point between the Aox and the cytochrome respiratory chain arises at the ubiquinone pool. These terminal oxidases can be identified by using respiratory inhibitors and are divided as different groups according to the sensitivities or resistances to the inhibitors. Alternative respiration is activated by stress stimuli factors that constrict the electron flow through the cytochrome pathway [137]. However, the roles and the compositions of these pathways are... 

Iron, like many of the micronutrients, is involved in enzymatic reactions. It is a constituent of cytochrome respiratory pigments found in animals, higher plants and microorganisms. These pigments that are involved in intracellular oxidations, are chemically much like hemoglobin, since they are complexes of iron, porphyrin and a protein. Cytochrome-c and the iron-porphyrin enzyme, cytochrome oxidase, both take part in cell respiration (Hewitt, 1951), and are probably also involved in photosynthesis. Iron is also required for fixation of elemental nitrogen in free-living and nodule bacteria (Nicholas, 1961). 

The operation of the cycle produces large quantities of the reduced forms of the nucleotides of adenine with nicotinamide (NAD and NADP) and ribo-flavine (FP). The regeneration of these coenzymes is effected by a transfer of electrons from the reduced forms to the oxygen of the atmosphere. In almost every kind of living cell, this transfer is mediated by some or all of the cytochrome respiratory chain (Section 5.4.3). Most of the organisms that lack all cytochromes have insignificant aerobic metabolism. Few enzymatic differences in the cycle have been demonstrated in mammals, but in the rat there is six times more aconitate hydratase in the heart than in skeletal muscle (Dixon and Webb, 1979). 

Oxidative phosphorylation is an aerobic process. The production of ATP is linked to the transport of electrons to an oxygen molecule by the cytochromic respiratory chain. This oxygen molecule is the final acceptor of the electrons. These reactions occur in the mitochondria. 

Electron Transport Between Photosystem I and Photosystem II Inhibitors. The interaction between PSI and PSII reaction centers (Fig. 1) depends on the thermodynamically favored transfer of electrons from low redox potential carriers to carriers of higher redox potential. This process serves to communicate reducing equivalents between the two photosystem complexes. Photosynthetic and respiratory membranes of both eukaryotes and prokaryotes contain stmctures that serve to oxidize low potential quinols while reducing high potential metaHoproteins (40). In plant thylakoid membranes, this complex is usually referred to as the cytochrome b /f complex, or plastoquinolplastocyanin oxidoreductase, which oxidizes plastoquinol reduced in PSII and reduces plastocyanin oxidized in PSI (25,41). Some diphenyl ethers, eg, 2,4-dinitrophenyl 2 -iodo-3 -methyl-4 -nitro-6 -isopropylphenyl ether [69311-70-2] (DNP-INT), and the quinone analogues,... 

This is the reverse Pasteur or Crabtree effect and is also known as glucose inhibition or cataboHte repression. In the presence of higher sugar concentrations, synthesis of respiratory enzymes such as cytochromes is inhibited. 

Atovaquone, a hydroxynaphthoquinone, selectively inhibits the respiratory chain of protozoan mitochondria at the cytochrome bcl complex (complex III) by mimicking the natural substrate, ubiquinone. Inhibition of cytochrome bcl disrupts the mitochondrial electron transfer chain and leads to a breakdown of the mitochondrial membrane potential. Atovaquone is effective against all parasite stages in humans, including the liver stages. 

Mitochondrial permeability transition involves the opening of a larger channel in the inner mitochondrial membrane leading to free radical generation, release of calcium into the cytosol and caspase activation. These alterations in mitochondrial permeability lead eventually to disruption of the respiratory chain and dqDletion of ATP. This in turn leads to release of soluble intramito-chondrial membrane proteins such as cytochrome C and apoptosis-inducing factor, which results in apoptosis. 

Another pathway is the L-glycerol 3-phosphate shuttle (Figure 11). Cytosolic dihydroxyacetone phosphate is reduced by NADFl to s.n-glycerol 3-phosphate, catalyzed by s,n-glycerol 3-phosphate dehydrogenase, and this is then oxidized by s,n-glycerol 3-phosphate ubiquinone oxidoreductase to dihydroxyacetone phosphate, which is a flavoprotein on the outer surface of the inner membrane. By this route electrons enter the respiratory chain.from cytosolic NADH at the level of complex III. Less well defined is the possibility that cytosolic NADH is oxidized by cytochrome bs reductase in the outer mitochondrial membrane and that electrons are transferred via cytochrome b5 in the endoplasmic reticulum to the respiratory chain at the level of cytochrome c (Fischer et al., 1985). 

In contrast to common usage, the distinction between photosynthetic and respiratory Rieske proteins does not seem to make sense. The mitochondrial Rieske protein is closely related to that of photosynthetic purple bacteria, which represent the endosymbiotic ancestors of mitochondria (for a review, see also (99)). Moreover, during its evolution Rieske s protein appears to have existed prior to photosynthesis (100, 101), and the photosynthetic chain was probably built around a preexisting cytochrome be complex (99). The evolution of Rieske proteins from photosynthetic electron transport chains is therefore intricately intertwined with that of respiration, and a discussion of the photosynthetic representatives necessarily has to include excursions into nonphotosynthetic systems. 

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). 

Narayan S, Dani HM, Misra UK. 1984. Effect of intratracheally administered DDT and endosulfan on pulmonary and hepatic respiratory cytochromes. Bull Environ Contam Toxicol 33 193-199. 

The cytochromes are iron-containing hemoproteins in which the iron atom oscillates between Fe + and Fe + during oxidation and reduction. Except for cytochrome oxidase (previously described), they are classified as dehydrogenases. In the respiratory chain, they are involved as carriers of electrons from flavoproteins on the one hand to cytochrome oxidase on the other (Figure 12-4). Several identifiable cytochromes occur in the respiratory chain, ie, cytochromes b, Cp c, a, and (cytochrome oxidase). Cytochromes are also found in other locations, eg, the endoplasmic reticulum (cytochromes P450 and h, and in plant cells, bacteria, and yeasts. 

Ubiquinone or Q (coenjyme Q) (Figure 12-5) finks the flavoproteins to cytochrome h, the member of the cytochrome chain of lowest redox potential. Q exists in the oxidized quinone or reduced quinol form under aerobic or anaerobic conditions, respectively. The structure of Q is very similar to that of vitamin K and vitamin E (Chapter 45) and of plastoquinone, found in chloroplasts. Q acts as a mobile component of the respiratory chain that collects reducing equivalents from the more fixed flavoprotein complexes and passes them on to the cytochromes. 

Functionally and strucmrally, the components of the respiratory chain are present in the inner mitochondrial membrane as four protein-lipid respiratory chain complexes that span the membrane. Cytochrome c is the only soluble cytochrome and, together with Q, seems to be a more mobile component of the respiratory chain connecting the fixed complexes (Figures 12-7 and 12-8). 

Barbiturates such as amobarbital inhibit NAD-hnked dehydrogenases by blocking the transfer from FeS to Q. At sufficient dosage, they are fatal in vivo. Antin cin A and dimercaprol inhibit the respiratory chain between cytochrome b and cytochrome c. The classic poisons H2S, carbon monoxide, and cyanide inhibit cytochrome oxidase and can therefore totally arrest respiration. Malonate is a competitive inhibitor of succinate dehydrogenase. 

Figure 12-8. Principles of the chemiosmotic theory of oxidative phosphorylation. The main proton circuit is created by the coupling of oxidation in the respiratory chain to proton translocation from the inside to the outside of the membrane, driven by the respiratory chain complexes I, III, and IV, each of which acts as a protonpump. Q, ubiquinone C, cytochrome c F Fq, protein subunits which utilize energy from the proton gradient to promote phosphorylation. Uncoupling agents such as dinitrophenol allow leakage of H" across the membrane, thus collapsing the electrochemical proton gradient. Oligomycin specifically blocks conduction of H" through Fq.

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

Superoxide is formed (reaction 1) in the red blood cell by the auto-oxidation of hemoglobin to methemo-globin (approximately 3% of hemoglobin in human red blood cells has been calculated to auto-oxidize per day) in other tissues, it is formed by the action of enzymes such as cytochrome P450 reductase and xanthine oxidase. When stimulated by contact with bacteria, neutrophils exhibit a respiratory burst (see below) and produce superoxide in a reaction catalyzed by NADPH oxidase (reaction 2). Superoxide spontaneously dismu-tates to form H2O2 and O2 however, the rate of this same reaction is speeded up tremendously by the action of the enzyme superoxide dismutase (reaction 3). Hydrogen peroxide is subject to a number of fates. The enzyme catalase, present in many types of cells, converts... 

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... 

The well-known fact that in irreversibly damaged cells, respiratory control is lost and is accompanied by oxidation of cytochromes a and as, as well as NADH (Taegtmeyer et al., 1985), was originally thoug it to be due to substrate deficiency (Chance and Williams, 1955) but may be due to an enzymatic defect resulting in an inability to metabolize NADH-linked substrates (Pelican etal., 1987). It seems likely therefore that return of function is dependent on preservation of mitochondrial membrane integrity, and the structure and activities of respiratory chain (R.C) complexes I-IV (Chance and Williams, 1955). 

---