Superoxide anion radical protein oxidation

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

Oxidative stress involves an imbalance between cellular reactive oxygen species (ROS) and antioxidant mechanisms that keep these in check. ROS include hydrogen peroxide (H202), superoxide anion radical (02- ), and the hydroxyl radical ( OH). 02 and OH are free radicals, that is, they possess an unpaired electron. As such, free radicals are extremely reactive and will seek an electron from nearby electron-rich macromolecules, for example, proteins, lipids, and DNA, which can lead to disruption of cellular functions. 

Most of the electrons donated to the mitochondrial electron transfer chain will react with oxygen to form water. However, a small percentage can leak and cause the formation of superoxide anion radicals, which, if not quickly detoxified, can lead to formation of other radicals and cause oxidative stress. Indeed the mitochondria are thought to be the main producer of ROS, which can damage proteins and nucleic acids and cause cellular damage. Mitochondria contain protective mechanisms that detoxify ROS (and so does the ceU), such as glutathione, superoxide dismutase, peroxiiedoxin, and thioredoxins, but they can be overwhelmed as an insult persists. 

As a consequence of these conditions, the levels of ROS such as superoxide anion radical (02 ), hydrogen peroxide (H2O2), and hydroxyl radical ("OH) are increased (Lushchak, 2014). They inactivate the mitochondrial enzymes, directly damage DNA, DNA repair enzymes, lipid peroxidation, cyt c release, and transcription factors leading to apoptosis/ceU death. Figure 3.9 illustrates the ROS/RNS-induced oxidative damage in proteins, lipids, and DNA. 

One of the important consequences of neuronal stimulation is increased neuronal aerobic metabolism which produces reactive oxygen species (ROS). ROS can oxidize several biomoiecules (carbohydrates, DNA, lipids, and proteins). Thus, even oxygen, which is essential for aerobic life, may be potentially toxic to cells. Addition of one electron to molecular oxygen (O,) generates a free radical [O2)) the superoxide anion. This is converted through activation of an enzyme, superoxide dismurase, to hydrogen peroxide (H-iO,), which is, in turn, the source of the hydroxyl radical (OH). Usually catalase... 

The majority of the enzyme-catalyzed reactions discussed so far are oxidative ones. However, reductive electron transfer reactions take place as well. Diaphorase, xanteneoxidase, and other enzymes as well as intestinal flora, aquatic, and skin bacteria—all of them can act as electron donors. Another source of an electron is the superoxide ion. It arises after detoxification of xenobiotics, which are involved in the metabolic chain. Under the neutralizing influence of redox proteins, xenobiotics yield anion-radicals. Oxygen, which is inhaled with air, strips unpaired electrons from these anion-radicals and gives the superoxide ions (Mason and Chignell 1982). 

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