O-Quinones Essay

The catechol estrogens can give rise to semiquinones and o-quinones by any oxidizing enzyme or transition metal ions such as Cu2＋ or Fe3 [66, 67, 68]. ROS including superoxide anion radicals and hydroxyl radicals is generated when semiquinones are converted to o-quinones and o quinones are reduced back to catechols and semiquinones. These metal ions and hydroxyl radicals are responsible for oxidative damage to DNA, lipids and proteins [69, 70]. Sulfation of E2 leads to decreased hormonal activities by facilitating their excretion. The metabolic clearance rate of a sulfonated steroid is very slow [71, 72]. Sulfonated estrogens display almost no ER binding affinity whereas desulfated estrogens may contribute to high levels of active estrogen in target tissues [73, 74]. Estrone sulfate is a major circulating metabolite and thought to be an important precursor of the …show more content…
However, excess ROS could chemically modify cellular macromolecules including DNA, proteins, carbohydrates, or lipids, thereby disrupting normal physiological functions of these biomolecules [76]. Oxidative metabolism of estrogen produces enough ROS in cells. Estrogen-mediated oxidative DNA damage in mammary gland epithelia includes the induction of 8-oxo-2'-deoxyguanosine, both in vitro and in vivo. The data may explain some of the estrogen-induced pro-oxidant effects previously reported in vivo [77]. In addition, this is the first report indicating that E2 is capable of inducing an increase in sensitivity to oxidative DNA damage through an ER-mediated mechanism [78]. Evidence for a one-electron oxidation of estradiol to its reactive phenoxyl radical intermediate is presented. The phenoxyl radical metabolite abstracts hydrogen from reduced glutathione generating the glutathione thiyl radical [79, 80].