Systems for the repair or replacement of damaged materials

Repair of oxidative damage must go on constantly, even under normal conditions of aerobic metabolism. For lipids, repair of peroxidized fatty-acid chains is catalyzed by phospholipase A2 , which recognizes the structural changes at the lipid-water interface caused by the fatty-acid hydroperoxide, and catalyzes removal of the fatty acid at that site. The repair is then completed by enzymatic reacylation. 6 Although some oxidatively damaged proteins are repaired, more commonly such proteins are recognized, degraded at accelerated rates, and then replaced. 6 For DNA, several multi-enzyme systems exist whose function is to repair oxidatively damaged DNA.6 For example, one such system catalyzes recognition and removal of damaged bases, removal of the damaged part of the strand, synthesis of new DNA to fill in the gaps, and religation to restore the DNA to its original, undamaged state. Mutant organisms that lack these repair enzymes are found to be hypersensitive to O2 , H20 2 , or other oxidants. 

One particularly interesting aspect of oxidant stress is that most aerobic organisms can survive in the presence of normally lethal levels of oxidants if they have first been exposed to lower, nontoxic levels of oxidants. This phenomenon has been observed in animals, plants, yeast, and bacteria, and suggests that low levels of oxidants cause antioxidant systems to be induced in vivo. In certain bacteria, the mechanism of this induction is at least partially understood. A DNA-binding regulatory protein named OxyR that exists in two redox states has been identified in these systems. 33 Increased oxidant stress presumably increases concentration of the oxidized form, which then acts to turn on the transcription of the genes for some of the antioxidant enzymes. A related phenomenon may occur when bacteria and yeast switch from anaerobic to aerobic metabolism. When dioxygen is absent, these microorganisms live by fermentation, and do not waste energy by synthesizing the enzymes and other proteins needed for aerobic metabolism. However, when they are exposed to dioxygen, the synthesis of the respiratory apparatus is turned on. The details of this induction are not known completely, but some steps at least depend on the presence of heme, the prosthetic group of hemoglobin and other heme proteins, whose synthesis requires the presence of dioxygen.