Cytochrome oxidase, also

Cytochrome oxidase also serves as a proton pump, so that the process of electron transfer is associated with the vectorial transfer of protons across the membrane, and thus contributes to the establishment of the proton gradient which is used to drive the synthesis of ATP. Cytochrome oxidase is located in the inner mitochondrial membrane of animal, plant and yeast cells (the eukaryotes) and in the cell membrane of prokaryotes. The arrangement is represented schematically in Figure 58. The complexity of cytochrome oxidase and the problems associated with its solubilization from the membrane have presented great obstacles to the elucidation of the structure and mechanism of the enzyme, but its importance has resulted in an enormous literature, which has been reviewed frequently.1296 1299... 

Cytochrome oxidase (also called complex IV) contains two cytochromes (cytochrome a and a3). Cytochrome a is paired with a copper atom, CuA, and cytochrome a3 is paired with a different copper atom, CuB. During electron... 

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. 

Electron carriers which contain iron (and in the case of cytochrome oxidase also copper) they undergo oxidation and reduction by electron transfer alone. These are the cytochromes, in which the iron is present in a haem molecule, and nonhaem iron proteins, sometimes called iron—sulphur proteins, because the iron is bound to the protein through the sulphur of the amino acid cysteine. Figure 3.19 shows the arrangement of the iron in non-haem iron proteins and the three different types of haem that occur in cytochromes ... 

Thus, Og and cytochrome c oxidase are the final destination for the electrons derived from the oxidation of food materials. In concert with this process, cytochrome c oxidase also drives transport of protons across the inner mitochondrial membrane. These important functions are carried out by a transmembrane protein complex consisting of more than 10 subunits (Table 21.2). 

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. 

CBD has no activity at the CBl or CB2 receptor. It is well known that CBD influences the activity of THC if co-administered [140]. Another effect of CBD is the inhibition of cytochrome oxidase [141], which inversely to its antagonistic activity strongly potentiates THC effects above a certain threshhold. CBD is also active as a mild antipsychotic [142] and was proposed as a treatment for anxiety and panic attacks. The mechanism is not fully understood, but it might be caused by an interference with the endocannabi-... 

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. 

Female NMRI mice were exposed to 100 ppm of hydrogen sulfide for 2 hours at 4-day intervals excitement was observed (Savolainen et al. 1980). Exposure also resulted in decreased cerebral ribonucleic acid (RNA), decreased orotic acid incorporation into the RNA fraction, and inhibition of cytochrome oxidase. An increase in the glial enzyme marker, 2, 3 -cyclic nucleotide-3 -phosphohydrolase, was seen. Neurochemical effects have been reported in other studies. Decreased leucine uptake and acid proteinase activity in the brain were observed in mice exposed to 100 ppm hydrogen sulfide for 2 hours (Elovaara et al. 1978). Inhibition of brain cytochrome oxidase and a decrease in orotic acid uptake were observed in mice exposed to 100 ppm hydrogen sulfide for up to 4 days (Savolainen et al. 1980). 

Mitochondrial DNA is inherited maternally. What makes mitochondrial diseases particularly interesting from a genetic point of view is that the mitochondrion has its own DNA (mtDNA) and its own transcription and translation processes. The mtDNA encodes only 13 polypeptides nuclear DNA (nDNA) controls the synthesis of 90-95% of all mitochondrial proteins. All known mito-chondrially encoded polypeptides are located in the inner mitochondrial membrane as subunits of the respiratory chain complexes (Fig. 42-3), including seven subunits of complex I the apoprotein of cytochrome b the three larger subunits of cytochrome c oxidase, also termed complex IV and two subunits of ATPase, also termed complex V. 

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