Cyanide metabolic processes

When the temperature of the solution is increased, then the current as well as the sodium transport rate increase far more than would correspond to simple diffusion or migration. When substances inhibiting metabolic processes are added to the solution, e.g. cyanide or the glycoside, ouabain,... 

Adverse effects on metabolic processes constitute a major mode of action of toxic substances. For example, cyanide ion bonds with ferricytochrome oxidase, a form of an enzyme containing iron(III) that cycles with ferrouscytochrome oxidase, containing iron(II), in the respiration process by which molecular oxygen is utilized, thus preventing the utilization of 02 and leading to rapid death. 

Cyanide bonds to the iron(III) of the ferricytochrome enzyme, preventing its reduction to iron(II) in the first of the two reactions above. The result is that ferrouscytochrome oxidase, which is required to react with 02, is not formed and utilization of oxygen in cells is prevented, leading to rapid cessation of metabolic processes. The decreased utilization of oxygen in tissue results in a... 

HCN, or cyanide, is relatively toxic and inhibits numerous metabolic processes in all organisms (for a review, see Solomonson, 1981). Due to the great... 

The acute toxicity of HCN and cyanide is a consequence of the affinity of these substances for various heavy metals, such as iron or copper, by forming cyano complexes. The effect on cytochromes, which results in an efficient inhibition of respiration, is most important. In addition, numerous other metabolic processes are affected (for a review, see Solomonson, 1981). The lefhal dose of cyanide for humans is considered to be about 1 mg per kg... 

Another important class of carbon compounds, the cyanides, contain the anion group C=N . Cyanide ions are extremely toxic because they bind almost irreversibly to the Fe(III) ion in cytochrome oxidase, a key enzyme in metabolic processes. Hydrogen cyanide, which has the aroma of bitter almonds, is even more dangerous because of its volatility (b.p. 26°C). A few tenths of 1 percent by volume of HCN in air can cause death within minutes. Hydrogen cyanide can be prepared by treating sodium cyanide or potassium cyanide with acid ... 

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. 

Both hydrogen cyanide (HCN) and cyanide salts (which contain CN ion) are rapidly acting poisons a dose of only 60-90 mg is sufficient to kill a human. Metabolically, cyanide bonds to iron(III) in iron-containing ferricytochrome oxidase enz5mie (see enzymes in Chapter 10, Section 10.6), preventing its reduction to iron(II) in the oxidative phosphorylation process by which the body utilizes O2. This prevents utilization of oxygen in cells, so that metabolic processes cease. 

A variety of systems are available to minimize the different, potentially destabilizing factors. For example, histones appear to stabilize DNA in the nucleus. Buffer systems minimize the impact of organic acids. Proteins are capable of binding trace metals, anions, and cations. Enzymatic systems are present which metabolize cyanide, sulfate, ammonia, peroxides, and superoxide. Mechanisms are available to dispose of carbon dioxide, and the heat generated by metabolic processes... 

Levels of Significant Exposure to Cyanide - Inhalation 2-2 Levels of Significant Exposure to Cyanide - Oral 2-3 Basic Processes Involved in the Metabolism of Cyanide 2-4 Minor Path for the Removal of Cyanide from the Body... 

Figure 2-3. Basic Processes Involved in the Metabolism of Cyanide... 

Ibrahim et al. 1963). Aiken and Braitman (1989) determined that cyanide has a direct effect on neurons not mediated by its inhibition of metabolism. Consistent with the view that cyanide toxicity is due to the inability of tissue to utilize oxygen is a report that in cyanide-intoxicated rats, arterial p02 levels rose, while carbon dioxide levels fell (Brierley et al. 1976). The authors suggested that the low levels of carbon dioxide may have led to vasoconstriction and reduction in brain blood flow therefore, brain damage may have been due to both histotoxic and anoxic effects. Partial remyelination after cessation of exposure has been reported, but it is apparent that this process, unlike that in the peripheral nervous system, is slow and incomplete (Hirano et al. 1968). The topographic selectivity of cyanide-induced encephalopathy may be related to the depth of acute intoxication and distribution of blood flow, which may result in selected regions of vascular insufficiency (Levine 1969). 

Radical formation is a requisite step in cytochrome P450 hydroxylations, and cytochrome P450-mediated hydroxylation proceeds by a stepwise process involving radical substrate intermediates. Metabolism of nitriles to release cyanide involves radical formation on the a-carbon, followed by subsequent hydroxylation to the corresponding cyanohydrin intermediate, which decomposes readily to release cyanide and the corresponding carbonyl-containing co-product. Cytochrome P450-mediated release of cyanide from nitriles is depicted in Scheme 4.4. 

The reason for the presence of the alternate pathway is not clear. One possible function is that when significantly increased levels of intermediates are needed during periods of high metabolic activity, their rate of synthesis is limited by the rate of the electron transport system. The alternate pathway may provide an unrestricted means of accelerating respiration and the production of the required intermediates. The alternative pathway s relationship to certain developmental processes supports this possibility. For example, cyanide inhibits the respiration of dormant tubers more than... 

OEHHA Office of Environmental Health Hazard Assessment OSHA Occnpational Safety and Health Administration Osteogenic sarcoma Cancer associated with bone structures Oxidation Chemical addition of oxygen to break down pollutants or organic waste, for example, destruction of chemical substances such as cyanides, phenols, and organic sulfur compounds in sewage by bacterial and chemical means Oxidative stress Process whereby the metabolic balance of a cell is disrupted by exposure to environmental substances, resulting in accumulation of free radicals, which can damage the cell... 

Cyanide poisoning is marked by metabolic acidosis and a large anion gap. The latter is a consequence of the blocked oxidative phosphorylation and the increased rate of glycolysis. Maduh et al (1990) showed that cyanide also affects and thus the pH of the tissues. In turn, the Ca transport process is disrupted, leading to a rise in cystolic [Ca ]. Acidification depolarizes the cell membrane and changes the potassium conductance. 

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