Enzyme cytochrome oxidase

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. 

The toxic effect of cyanide is attributed predominantly to the production of anoxia following inhibition of the metal-containing enzymes. The critical interaction appears to be the inhibition of the terminal respiratory chain enzyme, cytochrome oxidase as (containing iron) within the mitochondria. The enzyme is essential for the production of adenosine triphosphate (ATP). As a result, aerobic oxidative... 

Aoki C, Milner TA, Berger SB, Sheu K-FR, Blass JP, Pickel VM (1987a) Glial glutamate dehydrogenase ultrastructural localization and regional distribution in relation to the mitochondrial enzyme, cytochrome oxidase. 

Blood Agents are compounds that stop the transfer of oxygen from the blood system to the rest of the body by inhibiting the enzyme cytochrome oxidase. The lack of oxygen rapidly affects all body tissues, especially the central nervous system. Some Blood Agents will also cause lung membranes to swell and become filled with liquid (pulmonary edema). 

Because the cytochrome a3 complex works by oxidizing the earlier cytochromes at the expense of oxygen, it is sometimes referred to as if it were an enzyme, cytochrome oxidase. 

Copper is a mineral that is required for many essential enz)rmes. The respiratory electron transport chain contains an enzyme, cytochrome oxidase, that contains both heme groups and copper ions. Copper is therefore required in the diet for the function of this essential enzyme. Copper is also required by some of the enzymes that are responsible for the synthesis of connective tissue proteins. Seafood, vegetables, nuts, and meats such as liver are excellent sources of copper ions. The ESADDI for adults is 1.5-3.0 mg. Copper ions in high concentrations are toxic. In fact, mental retardation and death in early adolescence result from an inability to remove excess copper ions from the body. As everywhere in life, the balance of the system is critical to its function. 

There are other tetrapyrrole macrocycles found in nature besides protoporphyrin IX (Figure 1). Differences with the latter can be as simple as changes in the substituents on the porphyrin periphery, such as in heme a and heme a3, which are key components of the mammalian respiratory enzyme cytochrome oxidase (see Chapter 8.17). Other disparities can entail changes in the oxidation level of the macrocycle, such as the two-electron reduced heme d of cytochrome... 

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 toxicity of cyanide is attributed to its ability to inhibit enzyme reactions. The action of one such enzyme, cytochrome oxidase, essential for the respiration of cells is inhibited by cyanide ions. Cytochrome oxidase is a component of the mitochondrial electron transport system. It transfers electrons from cytochrome c to oxygen, forming water, while releasing sufficient free energy to permit the formation of adenosine 5 -triphosphate (ATP). The latter is essential for normal metabolic processes. Cyanide ion forms complexes with heavy metal ions such as iron and copper to stop electron transport and thus prevent ATP formation. Several enzyme reactions have been listed that cyanide can inhibit several enzyme reactions by forming complexes. 

This compound, similar to glycer-aldehyde, pyruvate, and alpha-ketoglutarate, trapped cyanide to form cyanohydrin, thus rapidly reactivating the enzyme cytochrome oxidase and restoring CN-inhibited mitochondrial respiration. The authors have reported this antidote to be effective especially in cases of CN-carbon monoxide smoke inhalation. 

By using a marker enzyme (cytochrome oxidase) we were able to calculate the amount of mt DNA per cell in impure mitochondrial fractions free of nuclear contaminants by measuring both the DNA concentration and the activity of cytocrome oxidase in the mitochondrial fraction and in the homogenate (Neubert, 1970), This procedure allowed measurement of the mt DNA content of embryonic cells (Table IV) it should be equally suitable for measurements with bone marrow samples, small amounts of tissue from organ cultures, or similar preparations. 

We have studied amino acid incorporation into mitochondrial proteins (CAP-sensitive and CH-insensitive) in vitro during late organogenesis in rats (days 11-14 of gestation). Because of microsomal contamination our data were based on the activity of a mitochondrial marker enzyme, cytochrome oxidase, (Table XIII). Protein synthesis in mitochondria... 

In conclusion, the morphological identification of each cell fraction should be completed by its biochemical characterization. This should include the determination of basic compounds (nitrogen, nucleic acids, and phospholipids) and the assay of specific reference enzymes (cytochrome oxidase, glucose-6-phosphatase, and acid phosphatase). 

Different aproaches have been proposed. Several biochemical markers of mitochondrial dysfunction have been characterized in Alzheimer s disease, especially a decrease in activity of the mitochondrial enzyme cytochrome oxidase in blood platelets. In rats given a chronic infusion of sodium azide, an inhibitor of cytochrome oxidase, both spatial and non-spatial learning impairment have been demonstrated [50]. 

A modified carbon paste electrode (CPE) using asolectin, cytochrome c, and cytochrome oxidase were applied for amperometric determination of cyanide [56]. The modified CP matrix mimics a biological membrane environment. The sensor, polarized at —0.15 V versus Ag/AgCl, generates the reduced form of cytochrome c, which in turn is oxidized by the enzyme cytochrome oxidase. The resulting current is related to the enzyme activity and is depressed by inhibitors of cytochrome oxidase such as cyanide. Concentrations of cyanide as low as 0.5 pM can be measured with half-maximal response at about 12 pM. The inhibition is reversible and reproducible (RSD = 4%), allowing cyanide determination for more than 2 months using the same probe. Possible use of this biosensor in flow systems was illustrated. 

The amount of copper in the body is 80-100 mg. Copper is a component of a number of oxido-reductase enzymes (cytochrome oxidase, superoxide dismutase, tyrosinase, uricase, amine oxidase). In blood plasma, it is bound to ceruloplasmin, which catalyzes the oxidation of Fe + to Fe +. This reaction is of great significance since it is only the Fe + form in blood which is transported by the transferrin protein to the iron pool in the liver. The daily copper requirement is 1-1.5 mg and it is supplied in a normal diet. Copper is even less desirable than iron during food processing and storage since it catalyzes many unwanted reactions. Cu +-Ions are taste bearing. The threshold value 2.4-3.8 mg/1 was determined with aqueous solutions of CuSOa or CuCl2. 

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