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Effect of Cyanide on ATP S ynthesis

Effect of Cyanide on ATP S ynthesis. Pui Tong HNSC 7210X Nutritional Biochemistry. What is Cyanide?. Cyanide is a chemical compound cyano group C Ξ N Most cyanides are highly toxic Cyanides are produced by certain bacteria, fungi and algae and are found in a number of plants

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Effect of Cyanide on ATP S ynthesis

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  1. Effect of Cyanide on ATP Synthesis Pui Tong HNSC 7210X Nutritional Biochemistry

  2. What is Cyanide? • Cyanide is a chemical compound cyano group CΞN • Most cyanides are highly toxic • Cyanides are produced by certain bacteria, fungi and algae and are found in a number of plants • Commonly used as poison for war or homicides • Many are rapidly absorbed via skin and respiratory and gastrointestinal tract.

  3. Oxidative phosphorylation via Electron Transport Chain

  4. Mechanism of Cyanide • Cyanide anion is an inhibitor of the enzyme cytochrome c oxidase • Cytochrome oxidase complex needed for reduction of oxygen to water • Therefore pathway of oxidative phosphorylation is inhibited and it halts the production of ATP

  5. Signs and symptoms • Intracellular hypoxia • Hypoventilation • Central nervous system manifestations • headache • Confusion • Anxiety • Paralysis • Seizures • Coma • Death

  6. Methods • Rat mesencephalic cell line (N27) was used • After treating the cells with • NaNO2 and/or the • NO scavenger 2-phenyl- 4,4,5,5 tetramethylimidazoline 1 oxy 3 oxide (PTIO) • intracellular NO was measured • Cellular oxygen consumption was monitored • Cellular cytochrome c oxidase (CcOX) activity was measured

  7. Results • Generation of NO from NaNO2 was rapid. • KCN rapidly inhibited oxygen consumption and reduced respiration • Pretreatment with NaNO2 inhibited the effect of KCN • Treatment of carboxy PTIO significantly reversed cyanide inhibition of oxygen consumption by NaNO2 • 10 min after addition of cyanide = ~48% inhibition of CcOX • Preincubation with NaNO2 reduced cyanide inhibition • Pretreatment with PTIO reversed the action of NaNO2

  8. Conclusion • Binding of cyanide to the CcOX can be reversed by antidotes that have high binding affinity for cyanide. • Mechanism of NaNO2 not entirely due to binding of cyanide via mHbbut in part by generation of NO as well. • NaNO2 acts a cyanide antidote by forming NO which displaces cyanide from the CcOX binding site. • The interaction of NO and cyanide at the CcOXheme center alters the kinetics of CcOX to favor O2 binding thus reactivating oxidative phosphorylation. • References: Hamel, Jillian. "A Review of Acute Cyanide Poisoning with a Treatment Update." Critial Care Nurse 31.1 (2011): 71-82. Web. 3 Dec. 2012. • Leavesley, Heather B., Li Li, Soma Mukhopadhyay, Joseph L. Borowitz, and Gary E. Isom. "Nitrite- Mediated Antagonism of Cyanide Inhibition of Cytochrome C Oxidase in Dopamine Neurons." Toxiocological Sciences 115.2 (2010): 569-76. Web. 3 Dec. 2012.

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