Cytochrome oxidase, mechanism

Fig. 4. A comparison of peroxidase, cytochrome c oxidase and cytochrome P-450 reaction mechanisms. Peroxidase mechanism adapted from that of Poulos[143], cytochrome P-450 mechanism adapted from that of Sligar [100], and cytochrome oxidase mechanism adapted from that of Babcock and Wikstrom[90]. RH, organic substrate for peroxidase and cytochrome P-450 (in the latter case the substrate is presumed to remain bound to the enzyme through most of the reaction cycle).

Figure 18.19. Cytochrome Oxidase Mechanism. The cycle begins with all prosthetic groups in their oxidized forms (shown in blue). Reduced cytochrome c introduces an electron that reduces Cug. A second reduced cytochrome c then...

Why has nature chosen this rather convoluted path for electrons in Complex 111 First of all. Complex 111 takes up two protons on the matrix side of the inner membrane and releases four protons on the cytoplasmic side for each pair of electrons that passes through the Q cycle. The apparent imbalance of two protons in ior four protons out is offset by proton translocations in Complex rV, the cytochrome oxidase complex. The other significant feature of this mechanism is that it offers a convenient way for a two-electron carrier, UQHg, to interact with the bj and bfj hemes, the Rieske protein Fe-S cluster, and cytochrome C, all of which are one-electron carriers. 

FIGURE 21.20 A model for the mechanism of O9 reduction by cytochrome oxidase. 

The mechanism of reduction of dioxygen by fully reduced cytochrome oxidase. Correlation of room and low temperature studies. G. M. Clore, Rev. Inorg. Chem., 1980,2, 343-360 (52). 

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-... 

The mechanism of hydrogen sulfide toxicity is in part similar to that of cyanide. Like cyanide, hydrogen sulfide can inhibit the enzyme cytochrome oxidase resulting in tissue hypoxia. Specific health effects are discussed in greater detail below. 

Nature has had a long time to perfect her inorganic chemistry, and understanding the mechanisms of enzymatic action can suggest ways for the inorganic chemist to develop corresponding in vitro catalysts. We shall show how knowledge of cytochrome oxidase and cytochrome P-450 has led to such possibilities. 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

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. 

In all protein-protein complexes studied to date in which cytochrome c has been a partner, it has been shown that the ET rates depend strongly on the reaction driving force. It follows that variations in the reorganization energy could control ET rates in these cases [12]. In redox enzymes with two or more active centers, ET between two centers could be turned on by lowering X at roughly constant — AG [1]. Indeed, a proposal has been advanced that this type of mechanism would be an efficient way to gate the electron flow in a redox-linked proton pump such as cytochrome oxidase [75]. 

Fig. 17.9 Model of the mechanism of Fe " oxidation by Thioba-cillusferrooxidans. PL-Fe phospholipid bound Fe x enzyme (unidentified) Ru rusticyane, a Cu-containing protein cyt c c-type cytochrome cyt ox cytochrome oxidase complex ATP adenosine 5 -triphosphate (Ghiorse Ehrlich, 1992 with permission).

NO also has cytotoxic effects when synthesized in large quantities, eg, by activated macrophages. For example, NO inhibits metalloproteins involved in cellular respiration, such as the citric acid cycle enzyme aconitase and the electron transport chain protein cytochrome oxidase. Inhibition of the heme-containing cytochrome P450 enzymes by NO is a major pathogenic mechanism in inflammatory liver disease. 

The mechanism underlying the toxicity of the cyanide ion is relatively straightforward and involves reversible binding to and inhibition of the cytochrome a-cytochrome a3 complex (cytochrome oxidase) in the mitochondria. 

The other major toxic effect of methanol is the ocular toxicity. Although formaldehyde might be formed locally in the retina, this seems unlikely, whereas formate is known to cause experimental ocular toxicity. The mechanism suggested involves inhibition by formate of cytochrome oxidase in the optic nerve. As the optic nerve cells have few mitochondria, they are very susceptible to this "histotoxic hypoxia,"... 

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