Enzyme CuZn superoxide dismutase

Orgotein, an enzyme (CuZn superoxide dismutase) that is present in all mammalian cells, is obtained from bovine liver by several steps, including chromatography. It can be given parenterally or topically. Reliable published clinical experience of its properties is limited. In Germany, marketing approval for orgotein was suspended because of severe reactions and deaths, mostly due to hypersensitivity (SEDA-18,107). 

Fig. 2. Effect of inhibitors of de novo RNA and protein synthesis and of the antioxidant enzymes CuZn-superoxide dismutase and catalase on PMA-induced accumulation of poly(ADPR) in human fibroblasts 3229 (for experimental conditions see text)...

Dameron, C.T. and Harris. E.D. (1987b) Regulation of aortic CuZn-superoxide dismutase with copper. Ceruloplasmin and albumin re-activate and transfer copper to the enzyme in culture. Biochem. J. 248 669-675. 

In addition, Zn can be part of heterodinuclear active sites such as CuZn superoxide dismutase, an enzyme that has been discussed in the Cu section. Here, we will describe the active site structure and, whenever possible, the postulated catalytic mechanism of representative members of the enzyme classes mentioned above. We will also address some very recent structural results concerning other less weU-studied Zn-enzymes. 

In contrast, antioxidant enzymes can efficiently counteract all UV-induced ROS (Aguilera et al. 2002). These enzymes are represented by superoxide dismutase (SOD), catalase and glutathione peroxidase as well as those involved in the ascorbate-glutathione cycle, such as ascorbate peroxidase, mono-dehydroascorbate reductase, dehydroascorbate reductase and glutathione reductase. One of the most important classes of antioxidant enzymes is the SOD family, which eliminate noxious superoxide radical anions. Different metalloforms of SOD exist (Fe, Mn, CuZn and Ni), which due to their intracellular localisation protect different cellular proteins (Lesser and Stochaj 1990). 

The three-dimensional structure of human extracellular superoxide dismutase (EC-SOD) is unknown. Studies of structure-function relationships have been severely limited by its poor production in mammalian cell lines and failure to be expressed in prokaryotic and yeast systems. In contrast, extra- and intracellular Cu- and Zn-containing superoxide dismutases (CuZn-SOD) are expressed very well in E. coli and yeast. CuZn-SOD is homologous to a large interior fragment of EC-SOD, but lacks its extra N-terminal and C-terminal domains. Fusions of either the N-terminal domain of EC-SOD or both the N- and C-terminal domains of EC-SOD to CuZn-SOD resulted in a domain-swapped enzyme that expressed well and whose characteristics resemble EC-SOD (Stenlund and Tibell, 1999). 

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 ... 

Small nuclear ribonucleoprotein particle Soil organic carbon store-operated channel Suppressors of cytokine signaling Superoxide dismutase CuZn-SOD enzyme (intracellular)... 

We believe that using the genetic approaches that were used to identify other metallochaperones to discover any Zn(II) metallochaperones in E. coli will not be successful. In yeast/ . coli there are less than ten copper-containing proteins 47), and most of these proteins are involved with oxygen/reactive oxygen species chemistry. In constrast, there could be almost 200 Zn(II)-metalloproteins that have numerous catalytic and structural roles 48). The choice of a deficient phenotype that could be linked directly to Zn(II) would be very challenging. The choice of superoxide dismutase deficiency (CuZn enzyme) would probably not be successful in E. coli since there are two other... 

The superoxide dismutases are a family of enzymes responsible for metaboHsing superoxide free radical (O2 ") to produce hydrogen peroxide and water. Three types of SOD are found in mammalian systems mitochondrial Mn-SOD, cytosolic CuZn-SOD, and extracellular SOD (Marklund 1984, Zelko et al. 2002). 

Copper-zinc superoxide dismutase (CuZn-SOD) inhibits cell-mediated oxidation of LDL, but transgenic mice overexpressing CuZn-SOD might have increased atherosclerotic lesion area (388). The role of copper in atherosclerosis is difficult to predict and the studies are conflicting copper is an intrinsic constituent of SOD and ceruloplasmin and a component of Lysyl oxidase (the enzyme involved in collagen synthesis, a major component of ECM). Also, copper ions catalyze oxidative modification of LDL in vitro and possibly in vivo (reviewed in ref. 389). 

A list of important chloroplast scavenging systems (in addition to peroxisome-located catalase) is presented in Table 1.1, together with the toxic species that they control. The function of the carotenoid pigments has been outlined already, and the inhibition of their production has severe toxic consequences (see Chapter 4 of this volume). The CuZn chloroplast enzyme superoxide dismutase is the first line of defense against chloroplast... 

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