Superoxide Radical and Superoxide Dismutases

Abstract

The metalloenzymes that have been named superoxide dismutases have several attributes. They are abundant, widely distributed, essential as a defense against oxygen toxicity; they are also unique among enzymes in that their natural substrate is an unstable free radical. They are evolution's answer to the biological production of the superoxide radical (0 2 ), This free radical, previously considered only in connection with the high energy irradiation of oxygenated aqueous media, is also produced under ordinary circumstances within respiring cells. The superoxide radical is intrinsically reactive and can furthermore engender other enormously reactive radicals and excited states which are potentially capable of destroying the delicate chemical architecture of the cell. The intermediates of oxygen reduction, i.e., O 2 , H 2 0 2 , and OH', are the primary cause of oxygen toxicity; the enzymes, which catalytically scavenge them or prevent their production, are the foremost defenses which limit that toxicity. H2~ and the catalases anc! peroxidases, which scavenge it, are discussed in other chapters of this volume. We shall devote ourselves to superoxide and the superoxide dismutases.

Purification, molecular cloning, and some properties of a manganese-containing superoxide dismutase from Japanese flounder (Paralichthys olivaceus)

“…Inefficient targeting of Mn-SOD caused mitochondria without their full defense system against superoxide radicals, leading to protein oxidation as well as mitochondrial DNA mutations (Rosenblum et al, 1996;Ambrosone et al, 1999). Thus, it is becoming increasingly clear that the mitochondria-targeting signal plays a crucial role in terms of Mn-SOD controlling dioxygen toxicity in the mitochondria (Fridovich, 1995;Richter et al, 1995). According to some reports, the mitochondria-targeting signal is characterized by the existence of some common basic amino acids and the insertion of several hydrophobic amino acids into these basic amino acids (Roise and Schatz, 1988;Wispe et al, 1989).…”

Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts

“…Manganese superoxide dismutase is the principal scavenger for superoxide in mitochondria (Fridovich, 1998). Since increased expression of MnSOD has been associated with improved survival of cells to doxorubicin (Hirose et al, 1993), we aimed to verify whether changes in the expression level of this protein played a role in the increased resistance of cyclin E-overexpressing fibroblast to doxorubicin.…”

Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

“…SOD also demonstrates an unusual enzyme kinetics whereby Its activity is increased almost indefinitely with increased substrate conce-t~tration and no apparent Km or Vmax (1,6). There is some controversy as to whether high SOD activity is desirable, because the dismutation product, H202, has a higher diffuseability and a longer half-life, and may become a source of "OH production (107). However, 02 can generate H202 independent of SOD in the cell by attacking the ion-sulfur protein (4Fe-4S) cluster, thereby releasing Fe(ll), which sets the stage for "OH production via the Fenton reaction or via Haber-Weiss reaction (1).…”

“…However, 02 can generate H202 independent of SOD in the cell by attacking the ion-sulfur protein (4Fe-4S) cluster, thereby releasing Fe(ll), which sets the stage for "OH production via the Fenton reaction or via Haber-Weiss reaction (1). This "cooperativity" between 02 and H202 is an important mechanism for cellular damage, particularly DNA damage (107). In this view, an elevation of SOD in response to heavy physical e~'xercise is probably not only desirable, but vital, given the proximity of 02 generation to mitochondrial DNA.…”