Cytoplasmic superoxide

Cytoplasmic superoxider dismutase toxic oxygen removal... 

Zinc usually binds to proteins via residues of cysteine and histidine. Sometimes, zinc is bound to residues of glutamate or aspartate. The zinc ion sometimes plays a catalytic role and sometimes a structural role. In the latter case, it helps maintain the three-dimensional structure or conformation of the protein. For example, carboxypeptidase A contains two atoms of zinc. One is required for catalytic activity and is boimd to cysteine and histidine. The other, which plays a structural role, is bound only to cysteine. Cytoplasmic superoxide dismutase is a dimer. It contains one atom of Cu " and one of Zn per subunit. The zinc is boimd via three residues of histidine and one residue of aspartate. It is buried deep within the enzyme and serves a structural role. The copper atom is bound via four residues of histidine. It resides close to the surface of the protein and participates in the chemistry of catalysis. 

Activated phagocytes can release superoxide anion into the extracellular fluid as well as leak it into the cytoplasm. Superoxide can give rise to hydrogen peroxide... 

Ou, X., Tang, L., McCrossan, M., Henkle-Diihrsen, K. and Selkirk, M.E. (1995) Brugia malayi localisation and differential expression of extracellular and cytoplasmic CuZn superoxide dismutases in adults and microfilariae. Experimental Parasitology 80, 515-529. 

Figure 12.2 Copper chaperone function, (a) Copper homeostasis in Enterococcus hirae is affected by the proteins encoded by the cop operon. CopA, Cu1+-import ATPase CopB, Cu1+-export ATPase CopY, Cu1+-responsive repressor copZ, chaperone for Cu1+ delivery to CopY. (b) The CTR family of proteins transports copper into yeast cells. Atxlp delivers copper to the CPx-type ATPases located in the post Golgi apparatus for the maturation of Fet3p. (c) Coxl7p delivers copper to the mitochondrial intermembrane space for incorporation into cytochrome c oxidase (CCO). (d) hCTR, a human homologue of CTR, mediates copper-ion uptake into human cells. CCS delivers copper to cytoplasmic Cu/Zn superoxide dismutase (SOD1). Abbreviations IMM, inner mitochondrial membrane OMM, outer mitochondrial membrane PM, plasma membrane PGV, post Golgi vessel. Reprinted from Harrison et al., 2000. Copyright (2000), with permission from Elsevier Science.

Protection from unwanted side products of oxygen reactions uses the cytoplasmic Cu/Zn superoxide dismutase and vesicular haem catalases as in all eukaryotes as... 

In bacteria (Escherichia coli), paraquat is concentrated, reduced to the monocation radical, and combines with molecular oxygen to produce the superoxide radical within the cell. Copper and iron are essential mediators in bactericidal effects. The cytoplasmic membrane is the target organelle in paraquat toxicity to E. coli, and extent of damage correlates positively with levels of these metals (Kohen and Chevion 1988). 

The radical anion superoxide 02 is a product of activated leukocytes and endothelial cells and has been postulated to be a mediator of isch-emia-reperfusion injury and inflammatory and vascular diseases. Various superoxide dismutase (SOD) enzymes are known Cu,Zn-SOD in the cytoplasm of eukaryotic cells, Mn-SOD in mitochondria, and Fe-SOD and Mn-SOD in prokaryotic cells. They catalyze the conversion of 02 into H202 and 02... 

XOR is a cytoplasmic enzyme and a ready source of electrons for transfer to molecular oxygen to form reactive oxygen species such as superoxide and peroxide. It is therefore thought to be involved in free radical-generated tissue injury and has been implicated in the pathogenesis of ischemia-reperfusion damage. Moreover, it has recently been implicated in the production of peroxynitrite (89), and carbonate radical anion (92), both potent biological oxidants. Its exact role in lipid peroxidation, inflammation, and infection needs... 

Frontotemporal dementia involves an early and primary degenerative process of frontal and/or temporal cortex. Several disorders fall under this rubric, such as Pick s disease and the dementia associated with amyotrophic lateral sclerosis (ALS). ALS is a degenerative disease of upper motor neurons that is sometimes accompanied by a frontal lobe dementia (Vercelletto et al. 1999 Abe et al. 1997). ALS has been associated with mutations in the free radical scavenging enzyme superoxide dismutase 1 (Price et al. 1997). Pick s disease is associated histologically with a loss of neurons and cytoplasmic Pick bodies in surviving neurons. 

Nitric oxide has major effects that are mediated by activation of cytoplasmic soluble guanylyl cyclase and stimulated production of cGMP, an important second messenger. In addition, nitric oxide can produce several reactive nitrogen derivatives by interaction with molecular oxygen and superoxide radicals (Table 19-2). These highly unstable molecules react with a variety of proteins, lipids, nucleic acids, and metals (especially iron) in cells (Davis, 2001). The remainder of this chapter discusses some of the second messenger-mediated effects of nitric oxide and the effects of inhibition of its production. 

In addition to catalase, the enzymes glutathione peroxidase and superoxide dismutase are important elements in the cellular defenses against free radical oxygen. Cytoplasmic activity of glutathione peroxidase was decreased in rats by 14 and 28 days of exposure to doses of 500-2,000 mg/kg/day DEHP (Elliott and Elcombe 1987 Perera et al. 1986) and superoxide dismutase activity was decreased by a 28 day exposure of rats to 1,000 and 2,000 mg/kg/day (Elliott and Elcombe 1987). Glutathione... 

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