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Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical Warfare (2008) - The Black Vault

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Cyanide PoisoningFig. 11-1. Likely detoxification reactions for cyanide are shown for this hypothetical cell. <strong>The</strong> enzyme detoxification systemsare as follows:1. Rhodanese: an intramitochondrial liver enzyme that catalyzes the transfer <strong>of</strong> sulfur from a donor molecule tocyanide to form thiocyanate. Rhodanese is the major pathway for cyanide detoxification.2. Mercaptopyruvate sulfurtransferases: a group <strong>of</strong> enzymes widely distributed in the body that catalyze the transfer<strong>of</strong> a sulfane sulfur atom from a donor molecule to a thiophilic acceptor substrate for the limitation <strong>of</strong> cyanide.3. Thiosulfate reductase: enzymes found in the liver, kidney, heart, brain, intestine, and testis that use electrons fromthiols, which in vivo probably use electrons from glutathione, to reduce the sulfane sulfur atoms <strong>of</strong> inorganicthiosulfate and organic thiosulfonate anions to the sulfide level. Sulfide production from these thiol-dependentreductases is thought to be used in the synthesis <strong>of</strong> Fe-S proteins.4. Cystathionase: enzymes widely distributed in the body that can transfer sulfur from one cysteine to another,generating thiocysteine and pyruvate. Transamination <strong>of</strong> cysteine leads to the production <strong>of</strong> thiosulfate and thelimitation <strong>of</strong> cyanide.5. Albumin: molecules that act like an enzyme in the detoxification <strong>of</strong> cyanide. Albumin molecules contain sulfursites that bind to and limit cyanide.ADP: adenosine diphosphateATP: adenosine triphosphateATCA: 2-aminothiazoline-4-carboxylic acidCN − : cyanide ionCNMetHb: cyanomethemoglobinCNO: cyanateDIDS: 4,4’-diisothiocyano-2,2’-disulfonic stilbeneDMAP: dimethylaminophenolDNP: deoxyribonucleoproteinEDERF: endothelium-derived relaxing factorHb: hemoglobinMedHb: methemoglobinPAPP: p-aminopropiophenoneR: reduction factorS: substrateDrawing: Courtesy <strong>of</strong> Steven I Baskin, PhD, and Fred Sidell, PhD, US Army Research Institute <strong>of</strong> <strong>Chemical</strong> Defense, AberdeenProving Ground, Md.375

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