Cyanide enzymes inhibited

Acrylonitrile is beheved to behave similarly to hydrogen cyanide (enzyme inhibition of cellular metaboHsm) (150) and is befleved to be a potential carcinogen (151). It can also affect the cardiovascular system and kidney and Hver functions (150). Eurther information on the toxicology and human exposure to acrylonitrile is available (152—154) (see Acrylonitrile). 

This type of effect can occur in all tissues and is caused by a metabolic inhibitor such as azide or cyanide, which inhibits the electron transport chain. Inhibition of one or more of the enzymes of the tricarboxylic acid cycle such as that caused by fluoroacetate (Fig. 6.7) also results in inhibition of cellular respiration (for more details of cyanide and fluoroacetate see chap. 7). 

Recent studies have shown that cyanide also inhibits the antioxidant defense enzymes (such as catalase, superoxide dismutase, and glutathione peroxidase) and stimulates neurotransmitter release. These effects of cyanide may also contribute to its acute toxicity. The prolonged energy deficit and the consequent loss of ionic homeostasis, which may result in activation of calcium signaling cascade and eventually cell injury, contribute to cyanide toxicity resulting from subacute exposure or in the postintoxication sequela. 

Cyanide reversibly binds the ferric iron associated with the cytochrome oxidase system, thereby inhibiting the mitochondrial respiratory chain. This results in an inability to adequately utilize oxygen and causes internal asphyxia . Cyanide combines with hemoglobin to form cyanhemoglobin, which does not transport oxygen. Cyanide also inhibits antioxidant enzymes such as catalase, superoxide di-smutase, and glutathione peroxidase. 

Cyanide forms a stable complex with the ferric ion of cytochrome oxidase enzymes, inhibiting cellular respiration. What is the connection between the management of cyanide poisoning and the drugs amyl nitrite and nitroprusside The Skill Keeper Answer appears at the end of the chapter. 

Most nitriles are moderate to highly toxic substances. The toxic action is attributed to the presence of the cyanide (—CN) group. Acrylonitrile and acetone cyanohydrin are extremely toxic, as they decompose to hydrogen cyanide in the body. The cyanide released inhibits enzymes that cause respiration in tissue. This prevents tissue cells from using oxygen. 

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. 

Cyanide salts and the colorless gaseous HCN are highly toxic and should be handled with care. The primary toxicity of CN" results from inhibition of cytochrome c oxidase (a key enzyme in the electron transport chain), which catalyzes the four electron reduction of dioxygen to Hp. The cyanide ligand inhibits the enzyme by occupying the binding site on one of the enzyme s iron centers. 

An amperometric biosensor based on immobilization of polyphenol oxidase (PPO) into Zn-Al layered double hydroxides, also called anionic clays, was applied for the determination of cyanide [60]. The detection of cyanide was performed via its inhibiting action on the PPO electrode. Measurement was carried out with 3,4-dihydroxyphenylacetic acid as enzyme substrate, the eirzymatically generated quinoid products being electroreduced at 0.2 V. An extremely sensitive detection limit (0.1 nM) was obtained for cyanide. Enzyme immobilization into anionic exchanger clay seems to cause an increase in cyanide inhibition effects because of anion accumulation in the clay matrix. 

T. M. Park, E. I. Iwuoha, M. R. Smyth, Development of a Sol-gel Enzyme Inhibition-based Amperometric Biosensor for Cyanide. Electroanalysis, 9 (1997) 1120-1123. 

Inhibitors of 5-AL synthetase [reaction (3)] are L-penicillamine and L-cysteine which are hypothesized to form a thiazolidine ring with the pyridoxal-P moiety. Cyanide also inhibits, perhaps by interacting with bound pyridoxal-P. Parachloromercuribenzoate (PCMB) inhibits by acting on the enzyme, not on suecinyl CoA 36). 

Cyanide binds with metal ions that are biological constituents of several enzymes. Most important of these is the Fe in c5rtochrome oxidase. The ceU requires this enz)mie to utilize oxygen and cyanide will inhibit its function and ultimately result in cell death (Dixon and Webb 1958). It wfll also inhibit methemoglobin that competes with cytochrome oxidase for the cyanide ion. This competition is the basis for the first-aid procedures estabUshed for cyanide poisoning. 

Chance, using the spectrophotometric method, found cyanide to inhibit the oxidatic reaction just as well as the peroxidatic reaction. He observed a small cyanide insensitive activity in presence of maganese but does not mention the effect of cyanide on autoxidation in the absence of enzyme described by Swedin and Theorell. 

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