Cu, Zn superoxide dismutase SOD

Imidazoles are of interest as bridging ligands particularly with regard to mimics of the active site of Cu-Zn superoxide dismutase (SOD). Structures with imidazolate bridges have been... 

If the concentration of Cu, Zn-superoxide dismutase (SOD) in a yeast cell is 10 pM, the total copper (bound and free) is 70 pM, and the dissociation constant for loss of Cu+ from SOD is 6 fM, what will be the concentration of free Cu+ within the cell If the cell volume is 10 11 liter, how many copper ions will be present in a single cell See Roe et al. (1999) Science 284, 805-808. 

Cu—Zn superoxide dismutases (SODs) [87,88] are abundant in eukaryotic cells and may serve to protect cells against the toxic effects of superoxide or deleterious oxy-products derived from 02 . The active site copper and zinc ions are 6.3 A apart and are bridged by a histidine imidazolate. In the oxidized form Cu(II) is roughly pentacoordinate, with four His N s and a water molecule. A highly conserved Arg residue is thought to stabilize Cu(II)-bound anions (e.g., Cu(II)—02 ) a redox reaction releases 02, generating Cu(I), which can reduce more 02 substrate to give peroxide and Cu(II). 

Fig. 7. A Structural representation of Cu-Zn superoxide dismutase (SOD) active site (from Ref. 31c). B X-band (left) (77K v = 9.2 GHz) (from Ref. 25) and Q-band (right) (173 K v = 35 GHz) (from Ref. 26) EPR spectra of bovine Cu-Zn SOD. C Optical absorption spectra of native...

As we will also see in Chapter 8, free copper levels are extremely low within cells because the copper is bound to a family of metallochaperones which are subsequently involved in the incorporation of copper into copper-containing proteins. The mechanism proposed for copper insertion into the Cu/Zn superoxide dismutase, SOD 1, is presented in Fig. 4.7, and appears to use an already-preformed Cu-binding site. The copper chaperone CCS acquires copper as Cu from a copper transporter and then docks with the reduced dithiol form of SODl (steps I... 

Antioxidant enzymes do not always protect us. There was great excitement when it was found that victims of a hereditary form of the terrible neurological disease amyotrophic lateral sclerosis (ALS see also Chapter 30) carry a defective gene for Cu / Zn-superoxide dismutase (SOD Eq. 16-27). This discovery seemed to support the idea that superoxide anions in the brain were killing neurons. However, it now appears that in some cases of ALS the defective SOD is too active, producing an excess of H2O2, which damages neurons. 

The SDEL algorithm has also been applied to more complicated systems, such as the wild type human Cu, Zn superoxide dismutase (SOD) dimer. SOD is a 153-residue, homodimeric, anti-oxidant enzyme that dismutates superoxide ion to hydrogen peroxide and oxygen [87]. It is an eight-strand, flattened, beta-barrel protein with one copper and one zinc ion per monomer [88]. There are over 100... 

The reversibility of radiation fibrosis in skin and subcutaneous tissues in response to antioxidants is supported by regression of indnration reported in a French non-randomized pilot study involving intramuscnlar administration of bovine liposomal Cu/Zn superoxide dismutase (SOD), 5 mg twice weekly for 3 weeks, to 34 patients with 42 distinct zones of superficial fibrosis. Softening of snbcutaneous induration was noted in 86% of fibrotic zones, with an actuarial response rate of 70% by 5 years. Complete regressions were noted in 7 of 42 (17%) of the fibrotic zones. Supportive data are reported with topical apphcations of SOD over a period of several months in 40 patients with fibrosis after postmastectomy radiotherapy for early breast cancer. These studies were not pursued after bovine spongiform encephalopathy (BSE) was recognized and bovine products withdrawn. 

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