| Comments |
P.443 right column: "In the 1950s, Gerschman et al. suggested that oxygen toxicity derives from the same events that underlie the toxicity of ionizing radiation: the formation of partially reduced reactive oxygen species (ROS)[ref 4]. The four-electron reduction series of O2 is depicted in Fig. 1a and shows that the addition of consecutive electrons generates superoxide (O2−), hydrogen peroxide (H2O2) and the hydroxyl radical (HO•). The lethal effects of ionizing radiation had recently been shown to derive from HO• radicals, so Gerschman's idea seemed plausible. It was not immediately obvious how intracellular O2 might obtain the three electrons that could reduce it to HO•, but catalases and peroxidases (enzymes that degrade H2O2) had long been recognized to be ubiquitous among aerobic organisms [ref 5] (Fig. 1b). The existence of these enzymes implied that organisms must somehow routinely encounter H2O2 and that, were it not scavenged, H2O2 would harm the cell. In 1969, McCord and Fridovich reported the existence of an enzyme that dismuted O2−, and so a similar inference was drawn for this molecule [ref 6] (Fig. 1b)." P.444 right column 3rd paragraph: "Flavoprotein autoxidation occurs when O2 adventitiously collides with the dihydroflavin of the reduced enzyme (FIG. 1c)." See note beneath figure |