Cytochrome heart

Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawaitoh K, Nakashima R, Yaono R and Yoshikawa S 1995 Structures of metai sites of oxidized bovine heart cytochrome c oxidase at 2.8 angstrom Science 269 1069-74... 

Cytochrome c oxidase (from bovine heart mitochondria). [9001-16-5] Mr 100,0007haeme,... 

Both attractive forces and repulsive forces are included in van der Waals interactions. The attractive forces are due primarily to instantaneous dipole-induced dipole interactions that arise because of fluctuations in the electron charge distributions of adjacent nonbonded atoms. Individual van der Waals interactions are weak ones (with stabilization energies of 4.0 to 1.2 kj/mol), but many such interactions occur in a typical protein, and, by sheer force of numbers, they can represent a significant contribution to the stability of a protein. Peter Privalov and George Makhatadze have shown that, for pancreatic ribonuclease A, hen egg white lysozyme, horse heart cytochrome c, and sperm whale myoglobin, van der Waals interactions between tightly packed groups in the interior of the protein are a major contribution to protein stability. 

FIGURE 21.9 Typical visible absorption spectra of cytochromes, (a) Cytochrome c, reduced spectrum (b) cytochrome c, oxidized spectrum (c) the difference spectrum (a) minus (b) (d) beef heart mitochondrial particles room temperature difference (reduced minus oxidized) spectrum (e) beef heart submitochondrial particles same as (d) but at 77 K. a- and /3- bauds are labeled, and in (d) and (e) the bauds for cytochromes a, h and c are indicated. 

L., and Deiscnhofer, J, 1997. The crystal strnctnrc of the cytochrome bci complex from bovine heart mitochondria. Science 277 60-66.])... 

FIGURE 21.14 All electrophoresis gel showing the complex subunit structure of bovine heart cytochrome c oxidase. The three largest subunits, I, II, and III, are coded for by mitochondrial DNA. The others are encoded by unclear DNA. (Photo kindly provided by Professor Roderick Capaldi)... 

In be complexes bci complexes of mitochondria and bacteria and b f complexes of chloroplasts), the catalytic domain of the Rieske protein corresponding to the isolated water-soluble fragments that have been crystallized is anchored to the rest of the complex (in particular, cytochrome b) by a long (37 residues in bovine heart bci complex) transmembrane helix acting as a membrane anchor (41, 42). The great length of the transmembrane helix is due to the fact that the helix stretches across the bci complex dimer and that the catalytic domain of the Rieske protein is swapped between the monomers, that is, the transmembrane helix interacts with one monomer and the catalytic domain with the other monomer. The connection between the membrane anchor and the catalytic domain is formed by a 12-residue flexible linker that allows for movement of the catalytic domain during the turnover of the enzyme (Fig. 8a see Section VII). Three different positional states of the catalytic domain of the Rieske protein have been observed in different crystal forms (Fig. 8b) (41, 42) ... 

Fig. 8. (a) Structure of the full-length Rieske protein from bovine heart mitochondrial bci complex. The catalytic domain is connected to the transmembrane helix by a flexible linker, (b) Superposition of the three positional states of the catalytic domain of the Rieske protein observed in different crystal forms. The ci state is shown in white, the intermediate state in gray, and the b state in black. Cytochrome b consists of eight transmembrane helices and contains two heme centers, heme and Sh-Cytochrome c i has a water-soluble catalytic domain containing heme c i and is anchored by a C-terminal transmembrane helix. The heme groups are shown as wireframes, the iron atoms as well as the Rieske cluster in the three states as space-filling representations. 

Chlorophyll, plastoquinone, and cytochrome are complicated molecules, but each has an extended pattern of single bonds alternating with double bonds. Molecules that contain such networks are particularly good at absorbing light and at undergoing reversible oxidation-reduction reactions. These properties are at the heart of photosynthesis. 

BUN, blood urea nitrogen CBC, complete blood cell count CNS, central nervous system CYP, cytochrome P-450 isoenzyme LFT, liver function test MAO, monoamine oxidase QTc, Q-T interval corrected for heart rate SCr, serum creatinine TMP-SMX, trimethoprim-sulfamethoxazole. 

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). 

Daidone, I., Amadei, A., Roccatano, D., Nola, A. D., Molecular dynamics simulation of protein folding by essential dynamics sampling folding landscape of horse heart cytochrome c, Biophys. J. 2003, 85, 2865-2871... 

The improvement of its activity and stability has been approach by the use of GE tools (see Refs. [398] and [399], respectively). A process drawback is the fact that the oxidation of hydrophobic compounds in an organic solvent becomes limited by substrate partition between the active site of the enzyme and the bulk solvent [398], To provide the biocatalyst soluble with a hydrophobic active site access, keeping its solubility in organic solvents, a double chemical modification on horse heart cytochrome c has been performed [400,401], First, to increase the active-site hydrophobicity, a methyl esterification on the heme propionates was performed. Then, polyethylene glycol (PEG) was used for a surface modification of the protein, yielding a protein-polymer conjugates that are soluble in organic solvents. 

FIGURE 4.2 Linewidth increase with temperature for an S = 1/2 system. The linewidth of a feature in the low-spin heme spectrum from cytochrome a in bovine heart cytochrome oxidase has been fit as a convolution of a constant component from inhomogeneous broadening and a temperature-dependent component from homogeneous broadening (Hagen 2006). (Reproduced by permission of The Royal Society of Chemistry.)... 

FIGURE 9.3 Linewidth as a function of microwave frequency. The linewidth (FWHH) of the low-field gj-feature is plotted versus the frequency in L-, S-, X-, and Q-band. The left-hand panel is for the ferric low-spin heme in horse heart cytochrome c, and the right-hand panel is for the [2Fe-2S] cluster in spinach ferredoxin. (Data from Hagen 1989.)... 

Figure 3.96 The effect of increasing time of exposure (as indicated) of a gold electrode once-modified with SSBipy to thiophenol on the cyclic voltammetry of horse heart cytochrome t (0.4mM). 20 mM sodium phosphate/0.1 M NaCI04 pH 7.0. Scan rate 20mVs l. From Hill...

K.D. Gleria, H.A.O. Hill, V.J. Lowe, and D.J. Page, Direct electrochemistry of horse-heart cytochrome c at amino acid-modified gold electrodes. J. Electroanal. Chem. 213, 333-338 (1986). 

C. Hinnen, R. Parsons, and K. Niki, Electrochemical and spectroreflectance studies of the adsorbed horse heart cytochrome c and cytochrome c3 from D. vulgaris, miyazaki strain, at gold electrode. J. Electroanal. Chem. 147, 329-337 (1983). 

Such a process is supposed to occur within the limits of Q-cycle mechanism (Figure 23.2). In accord with this scheme ubihydroquinone reduced dioxygen in Complex III, while superoxide producers in Complex I could be FMN or the FeS center [12]. Zhang et al. [24] also suggested that the Q-cycle mechanism is responsible for the superoxide production by the succinate-cytochrome c reductase in bovine heart mitochondria and that FAD of succinate dehydrogenase is another producer of superoxide. Young et al. [25] concluded that, in addition to Complex III, flavin-containing enzymes and FeS centers are also the sites of superoxide production in liver mitochondria. 

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

As described earlier, superoxide is a well-proven participant in apoptosis, and its role is tightly connected with the release of cytochrome c. It has been proposed that a switch from the normal four-electron reduction of dioxygen through mitochondrial respiratory chain to the one-electron reduction of dioxygen to superoxide can be an initial event in apoptosis development. This proposal was supported by experimental data. Thus, Petrosillo et al. [104] have shown that mitochondrial-produced oxygen radicals induced the dissociation of cytochrome c from bovine heart submitochondrial particles supposedly via cardiolipin peroxidation. Similarly, it has been found [105] that superoxide elicited rapid cytochrome c release in permeabilized HepG2 cells. In contrast, it was also suggested [106] that it is the release of cytochrome c that inhibits mitochondrial respiration and stimulates superoxide production. 

O Donnell et al. [70] found that LOX and not cyclooxygenase, cytochrome P-450, NO synthase, NADPH oxidase, xanthine oxidase, ribonucleotide reductase, or mitochondrial respiratory chain is responsible for TNF-a-mediated apoptosis of murine fibrosarcoma cells. 15-LOX activity was found to increase sharply in heart, lung, and vascular tissues of rabbits by hypercholesterolemia [71], Schnurr et al. [72] demonstrated that there is an inverse regulation of 12/15-LOXs and phospholipid hydroperoxide glutathione peroxidases in cells, which balanced the intracellular concentration of oxidized lipids. 

---