Cytochrome oxidase-inhibiting cyanide

Usefulness of various biochemical indicators of cyanide poisoning, such as cytochrome oxidase inhibition (Gee 1987), estradiol and thyroxine levels in fish plasma (Ruby et al. 1986, 1993a), and pituitary gland histology (Ruby et al. 1993b)... 

The toxin, amygdalin, releases hydrocyanic acid. Thus, toxicity is similar to cyanide, and is dose-related. Cytochrome oxidase inhibition interrupts electron transport and oxygenation at the cellular level. 

The basic aim of rapid detoxification of cyanide is prevention or reversal of inhibition of cytochrome oxidase by cyanide. This is usually facilitated by providing a large pool of ferric iron in the form of methemoglobin to complex cyanide. Cyanide preferentially competes with the Fe + of methemoglobin as compared with that of cytochrome oxidase and eventually binds with the former to form cyanmethemoglobin. Thereby, the activity of inhibited cytochrome oxidase is restored (Baskin et al., 1992). The various methemoglobin inducers used as cyanide antidotes are discussed. 

Amine A, Alafandy M, Kauffmann J, Pekli MN (1995) Cyanide determination using an amperometric biosensor based on cytochrome oxidase inhibition. Anal Chcan 67 2822-2827... 

Barbiturates such as amobarbital inhibit NAD-hnked dehydrogenases by blocking the transfer from FeS to Q. At sufficient dosage, they are fatal in vivo. Antin cin A and dimercaprol inhibit the respiratory chain between cytochrome b and cytochrome c. The classic poisons H2S, carbon monoxide, and cyanide inhibit cytochrome oxidase and can therefore totally arrest respiration. Malonate is a competitive inhibitor of succinate dehydrogenase. 

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. 

Smith L, Kruszyna H, Smith RP. 1977. The effect of methemoglobin on the inhibition of cytochrome c oxidase by cyanide, sulfide or azide. Biochem Pharmacol 26 2247-2250. 

In higher plants, elevated cyanide concentrations inhibited respiration (through iron complex-ation in cytochrome oxidase) and ATP production and other processes dependent on ATP, such as... 

Drinking water, 1000 mg KCN/L, exposure for 40 days Marked inhibition of cytochrome oxidase activity in liver, brain, and blood increased cyanide concentrations in all tissues inhibition of rhodanese activity diminished labile sulfur tissue levels 43... 

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. 

Stannard JN, Horecker BL. 1948. The in vitro inhibition of cytochrome oxidase by azide and cyanide. 

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