Hemoglobin
Carbon monoxide has a higher diffusion coefficient compared to oxygen, and the main enzyme in the human body that produces carbon monoxide is heme oxygenase, which is located in nearly all cells and platelets. Most endogenously produced CO is stored bound to hemoglobin as carboxyhemoglobin. The simplistic understanding for the mechanism of carbon monoxide toxicity is based on excess carboxyhemoglobin decreasing the oxygen-delivery capacity of the blood to tissues throughout the body. In humans, the affinity between hemoglobin and carbon monoxide is approximately 240 times stronger than the affinity between hemoglobin and oxygen. However, certain mutations such as the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for carbon monoxide than oxygen resulting in systemic carboxyhemoglobin reaching a sustained level of 16% COHb.Hemoglobin is a tetramer with four prosthetic heme groups to serve as oxygen binding sites. The average red blood cell contains 250 million hemoglobin molecules, therefore 1 billion heme sites capable of binding gas. The binding of carbon monoxide at any one of these sites increases the oxygen affinity of the remaining three sites, which causes the hemoglobin molecule to retain oxygen that would otherwise be delivered to the tissue; therefore carbon monoxide binding at any site may be as dangerous as carbon monoxide binding to all sites. Delivery of oxygen is largely driven by the Bohr effect and Haldane effect.
In 1884, an article appeared in Scientific American describing the use of a carbon monoxide gas chamber for slaughterhouse operations as well as euthanizing a variety of animals.As part of the Holocaust during World War II, the Nazis used gas vans at Chelmno extermination camp and elsewhere to murder an estimated over 700,000 people by carbon monoxide poisoning. This method was also used in the gas chambers of several death camps such as Treblinka, Sobibor, and Belzec. Gassing with carbon monoxide started in Action T4. The gas was supplied by IG Farben in pressurized cylinders and fed by tubes into the gas chambers built at various mental hospitals, such as Hartheim Euthanasia Centre. Exhaust fumes from tank engines, for example, were used to supply the gas to the chambers.Recently, carbon monoxide gas chambers have been used to facilitate capital punishment exemplified by execution practices at the San Quentin State Prison. Physiology
Carbon monoxide is produced naturally by many physiologically relevant enzymatic and non-enzymatic reactions best exemplified by heme oxygenase catalyzing the biotransformation of heme (an iron protoporphyrin) into biliverdin and eventually bilirubin. Aside from physiological signaling, most carbon monoxide is stored as carboxyhemoglobin at non-toxic levels below 3% HbCO. Therapeutics
Small amounts of CO are beneficial and enzymes exist that produce it at times of oxidative stress. A variety of drugs are being developed to introduce small amounts of CO, these drugs are commonly called carbon monoxide-releasing molecules.