Accepting a pair of electrons that have antiparallel spin so as
Accepting a pair of electrons that have antiparallel spin so as to fit into the two vacant spaces of O2. This tends to make O2 only accept one electron at a time and thus react sluggishly with non-radicals. Thus O2 is the most stable state of oxygen. Superoxide (O2 ) has one more electron than O2. Since only one electron is unpaired in O2 , it is simpler for it to accept an electron and is thus more reactive than O2. However, O2 is still not a very reactive radical; in the presence of H+ or HO2?it can reduce O2 to H2O2 or be oxidized to O2. Another term that is often used is `reactive oxygen species’ (ROS). This term includes radicals as well as chemicals that can take part in radical type reactions (i.e. gain or loose electrons), but are not true radicals in that they do not have unpaired electrons. Examples of non-radical ROS include hydrogen peroxide (H2O2), hypochlorous acid (HOCl), ozone (O3) and singlet oxygen (1gO2). An important product of the two radicals O2 and NO is peroxynitrite (ONOO?; this reaction occurs at a diffusion limited rate [16,17]. Although not a radical itself, ONOO?can result in cytotoxic processes, including lipid peroxidation, the formation of nitrotyrosine residues that can inactivate enzymes, depletion of glutathione, and DNA injury. Besides oxygen-based radicals, there are also reactive nitrogen species such as nitric oxide (NO) and nitrogen dioxide (NO2), sulfur based molecules such as thinyl (RS) and perthinyl (RSS), as well as carbon centered molecules such as trichloromethyl (CCl3?, which is a product of metabolism of carbon tetrachloride (CCl4) [15].In phagocytic cells the major source of O2 is a multicomponent oxidase called NAD(P)H oxidase [23,24]. In response to membrane signals this complex produces a burst of O2 that is important for killing invading microorganisms. Genetic mutations in components of the complex result in chronic granulomatous disease, which is characterized by repeated infections. There are at least five components to the complex. Two, p22phox (phox stands for phagocyte associated oxidase) and gp91phox (subsequently called NOX2) are found in membranes [25,26]. NOX2 is the component that produces O2 . The complex is activated when the cytosolic component p67phox is transported to the membrane complex by the transporter molecule p47phox [27]. The attachment of p67phox to the membrane complex results in a conformational PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27465830 change in p22phox that exposes the active site on NOX2. The small g-protein Rac also contributes to the activity of the enzyme and transmits membrane signals to the complex. Recently, a family of non-phagocytic NOXs with the same basic components as the phagocytic type have been identified in numerous types of cells, including vascular smooth muscle, endothelial, skeletal muscle, fibroblast, and mesangial cells [28-30]. The non-phagocytic form produces much lower amounts of O2 compared to the phagocytic form but is constitutively active. O2 is also produced by a number of metabolically active enzymes as part of their normal function or when there is inadequate substrate. For example, cytochrome P450 enzymes can produce O2 as a side reaction when they breakdown target molecules [15]. Nitric oxide synthases, the family of enzymes that produce NO, produce O2 when the substrates ACY-241 custom synthesis L-arginine or co-factor tetrahydropteridines are insufficient [21,31,32]. O2 can also be produced by cyclooxygenase as part of arachidonic acid metabolism. O2 even can be produced th.
