Carbon monoxide (CO) is a molecule that has been extensively studied and much maligned since the discovery of its biological role as an asphyxiate by the French physiologist Claude Bernard in 1857. Bernard determined that CO produces asphyxia by reversibly binding to hemoglobin (1). In 1895, Haldane demonstrated that elevated partial pressures of oxygen antagonized binding of CO to hemoglobin and that experimental animals exposed to lethal CO poisoning survived when a large amount of oxygen was dissolved in their blood plasma (2). In 1944, Roughton and Darling reported that carboxyhemoglobin (COHb) shifted the oxygen-dissociation curve to the left due to the increased binding affinity of the unoccupied heme groups for oxygen (3). This of course made oxygen unloading at the tissue level more difficult. These early studies set the framework for explaining the mechanism of CO poisoning as being due to hypoxia at the tissue level. In 1949, Sjorstrand discovered that endogenously produced CO comes from the degradation of hemoglobin released during erythrocyte turnover (4). Coburn and associates reported the same findings in their work in 1967(5). In 1969, Tenhunen et al. described heme oxygenase (HO) as the enzyme responsible for the production of endogenous CO. They demonstrated that HO catalyzed the reaction that converted hemoglobin to biliverdin with CO and free iron as byproducts (6). There are three different isoforms of HO, of Whalen et al.94.
|Original language||English (US)|
|Title of host publication||Therapeutic Targets in Airway Inflammation|
|Number of pages||8|
|State||Published - Jan 1 2003|
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