Cytoplasmic superoxide dismutase

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. 

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... 

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... 

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. 

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... 

Two different superoxide dismutases (SODs) are found in mammalian tissues a Cu/Zn-containing enzyme which is found in the cytoplasm of most cells, and a further Mn-containing enzyme present within the mitochondrial compartment [1], Both enzymes catalyse the same reaction ... 

The general acceptance of free radicals in biological systems did not occur until the discovery (Mila) of superoxide dismutase (SOD), of which there are two enzymes, cytoplasmic CuZn-SOD and mitochondrial Mn-SOD. These enzymes catalyze the following reaction ... 

The Oj" is transformed to H2O2 by the superoxide dismutase (SOD), the enzyme present in the cytoplasm of most mammalian cells and in the extracellular fluids. 

Superoxide dismutase The major intracellular antioxidant enzyme in aerobic cells, the Cu-Zn form in the cytoplasm and the manganese form in the mitochondria, reduces superoxide radicals to hydrogen peroxide very rapidly and specifically. 

Fig. 9. Copper activation of Acel induces expression of three genes in Saccharo-myces cerevisiae. Crs5 and Cupl encode metallothionein-like molecules that buffer the cytoplasmic Cu concentration. Sodl is a Cu-buffering molecule in addition to its role as a superoxide dismutase.

Fig. 1. Schematic overview of copper trafficking and homeostasis inside the yeast cell. The actions of Mad and Ace 1, copper-dependent metalloregulatory transcription factors, control the production of copper import [copper transporter (Ctr) and reductase (Fre)] and detoxification/sequestration [metallothionein (MT)] machineries, respectively. Three chaperone-mediated delivery pathways are shown. Atxl shuttles Cu(I) to the secretory pathway P-type ATPase Ccc2 (right). CCS delivers Cu(I) to the cytoplasmic enzyme copper-zinc superoxide dismutase (SOD) (left). Coxl7 shuttles Cu(I) to cytochrome c oxidase (CCO) in the mitochondria (bottom). Mitochondrial proteins Scol and Sco2 may also play a role in copper delivery to the CuA and CuB sites of CCO. Copper metabolism and iron metabolism are linked through the actions of Fet3, a copper-containing ferroxidase required to bring iron into the cell (lower right) (see text).

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