Free radicals Superoxide

Tissues are protected from oxygen toxicity caused by the superoxide free radical by the specific enzyme superoxide dismutase. 

Fukuzawa, K. Gebicki, J. M. Oxidation of alpha-tocopherol in micelles and liposomes by the hydroxyl, perhydroxyl, and superoxide free radicals. Arch. Biochem. Biophys. 1983, 226, 242-251. 

Figure 5.2. Pathways of oxygen reduction. The sequential reduction of molecular oxygen, ultimately to water, is shown. Abbreviations 02 % superoxide free radical H202, hydrogen peroxide OH, hydroxide ion -OH, hydroxyl free radical e, electron H+, hydrogen ion. Singlet states of oxygen are also shown as i +02and Ag02.

It is important to note that the oxidation produces the superoxide free radical. Since it is toxic, the radical produced in reaction (a) must be removed. This is done in a reaction catalysed by superoxide dismutase, which produces hydrogen peroxide. However, this also must be removed (see Appendix 9.6 for discussion of free radicals). Removal of hydrogen peroxide is achieved in a reaction with reduced glutathione, catalysed by glutathionine peroxidase. 

Huie, R. E., and Padmaja, S. (1993). The reaction rate of nitric oxide with superoxide. Free Radicals Res. Commun. 18, 195-199. 

Figure 2.9. Glucose can enolize and reduce transition metals thereby generating superoxide free radicals (02" ), hydroxyl radicals ( OH), hydrogen peroxide (H202) and reactive dicarbonyl compounds. Adapted with permission from Wolff, S. P. (1996). Free radicals and glycation theory. In The Maillard Reaction. Consequences for the Chemical and Life Sciences, Ikan, R., ed., John Wiley Sons, Chichester, UK, 73-88.

Cellular Activation. Chemokines are potent cell activators after binding to the appropriate G protein-linked, seven-transmembrane spanning receptors, chemokines elicit transient intracellular calcium flux, actin polymerization, oxidative burst with release of superoxide free radicals, exocytosis of secondary granule constituents, and increased avidity of integrins for their adhesion molecules (Dl, E2). 

The enzyme removes the toxic superoxide free radical by the following pathway [CuZn]n+ + 02 - [CuZn](n 1)+ + 02... 

Misra, H.P. 1974. Generation of superoxide free radical during the auto-oxidation of thiols. J. Biol. Chem. 249, 2151-2155. 

From the known chemical properties of superoxide free radicals and hydrogen peroxide, it is unlikely that these two species will react directly with the range of biomolecules found in synovial fluid. It is more likely, particularly for superoxide radicals, that they will instead participate in redox reactions with complexes of metal ions such as iron and copper, although reaction with phenolic compounds cannot be excluded. It has been proposed therefore that synovial fluid, in particular hyaluronic acid, can be degraded in vivo through an iron-catalysed Haber-Weiss reaction. 

M27. Mossine, V. V., Linetsky, M., Glinsky, G. V., Ortwerth, B. J., and Feather, M. S., Superoxide free radical generation by Amadori compounds The role of acyclic forms and metal ions. 

Ascorbic Acid as a Scavenger of Superoxide, Hydroxyl Radical and Singlet Oxygen. The superoxide free radical reacts with ascorbic acid according to the equation ... 

Superoxide free radical (OT ) and hydrogen peroxide are continuously produced in vivo. In normal circumstances, electron leakage from electron transport chains, such as those in mitochondria and the endoplasmic reticulum, to molecular oxygen can generate the superoxidation radical... 

Antitumor antibiotic activated to an alkylating agent cross-links DNA inhibits DNA and RNA synthesis superoxide free radicals may produce DNA strand breaks... 

SOD played an important role in protecting the stability of the membrane system because it scavenged 02 radicals (superoxide free radicals). The effect of SOD is to protect chlorophyll from photooxidation at low temperature (16), thus it causes accumulation of chlorophyll in leaves under light. 

Elstner EF, Staffer C, Heupel A (1975) Determination of superoxide free radical ion and hydrogen peroxide as products of photosynthetic oxygen reduction. Z Naturforsch 30c 53-57 Emmel T, Sand W, Konig WA, Bock E (1986) Evidence for the existence of a sulphur oxygenase in Sulfolobus brierleyi. J Gen Microbiol 132 3415-3420 Ensign SA, Hyman MR, Arp DJ (1993) In vitro activation of ammonia monooxygenase from Nitrosomonas europaea by copper. J Bacteriol 175 1971-1980 Erickson RH, Hooper AB (1972) Preliminary characterization of variant CO-binding heme protein from Nitrosomonas. Biochim Biophys Acta 275 231-244 Erickson RH, Hooper AB, Terry KR (1972) Solubilization and purification of cytochrome a, from Nitrosomonas. Biochim Biophys Acta 283 155-166 Evans MCW, Buchanan BB, Amon DI (1966) A new ferredoxin-dependent carbon reduction cycle in a photosynthetic bacterium. Proc Natl Acad Sci USA 55 928-934 Falk JE (1964) Porpyrins and metalloporphyrins. Elsevier, Amsterdam... 

The superoxide free radical thus generated, 02, is very reactive and can damage enzymes, membrane lipids, and nucleic acids. Antimycin A, an inhibitor of Complex 111, may act by occupying the Q, site (Fig. 19-11), thus blocking the Q cycle and prolonging the binding of Q to the Qp site this would increase the likelihood of superoxide radical formation and cellular damage. From... 

It has been known for a long time that most of the flavonoids and their derivatives are principles capable of capturing free oxygen radicals, peroxides of fatty acids as well as hydroxyl groups. The capture of superoxide free radicals has been evidenced by the formation of trans-trans hydroperoxides of linoleic acid by flavonoids [173, 174]. The capture of hydroxyl radicals responsible of numerous cell degradations is what indicates its relation with factors of cellular protection. 

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