Manganese-containing SOD

SOD comprises a family of metalloproteins primarily classified into four groups copper, zinc-containing SOD (Cu, Zn-SOD), manganese-containing SOD (Mn-SOD), iron-containing SOD (Fe-SOD) and nickel-containing SOD (Ni-SOD). In the following studies, we will only focus on the uses of the former three kinds of SODs to construct SOD-based 02 biosensors since the last one, Ni-SOD, is not commercially available. 

In the literature there are only few studies on the water-exchange processes of the manganese(II) species in general (33,38- 1), and the only seven-coordinate Mn(II) complexes studied are [Mn(EDTA) (H20)] and its derivatives (38,39,42,43). Such studies are essential for understanding the mechanism of the manganese-containing SOD mimetics. The volume of activation for the water-exchange reaction... 

CD spectroscopy has also been used to study the metal-binding and reactivity properties of iron- and manganese-containing SODs. These enzymes metabolize the superoxide ion radical O2 into molecular oxygen and hydrogen peroxide. The Fe- and Mn-SOD enzymes are strictly metal specific. Jackson and Brunold show that, despite the fact that Fe replacement of Mn in the Mn-SOD enzyme [(Mn Fe)-SOD] results in an inactive enzyme, the CD spectrum of wild-type Fe-SOD and (Mn - Fe)-SOD are remarkably similar. This suggests that the destroyed enzyme activity, upon replacement of the metal, does not occm via distortion of the enzyme active site. 

Human cells have a manganese-containing SOD (Mn-SOD) in the mitochondria, whereas the copper- and zinc-containing SOD (Cu,Zn-SOD) is primarily present in the cytosol [39]. Two enzyme systems exist to catalyze the breakdown of H202. Firstly, the enzyme catalase, which is located in the peroxisomes, converts H202 into H20 and 02 (Eq. 2) [35]. 

P. berghei isolated from mouse red blood cells also contains a cyanide-sensitive SOD activity. Plasmodial and mouse enzymes are indistinguishable electrophoretically. These results suggest that the malarial cyanide-sensitive SOD may be entirely of host origin and stored by the parasite. Accordingly, plasmodium isolated from mouse red blood cells contain mouse cyanide-sensitive SOD, whereas rat-derived parasites contain the rat enzyme (78). Another, peroxide-sensitive, apparently manganese-containing SOD, has been described in P. falciparum (79). Two Babesia species (B. hylomysci and... 

Iron SOD s are found in prokaryotes and plants Manganese and iron enzymes are phylogenetically older and they show great sequence homologies which are different from those of the Cu2Zn2superoxide dismutases Compared to the latter species, iron and manganese containing SOD s have received much less attention. 

Superoxide dismutase (SOD) is a widely distributed enzyme that exists in a variety of forms. The copper-zinc enzyme (Cu,ZnSOD) is primarily located in the cytosol of eukaryotic cells. Mitochondria contain, in the matrix space, a distinctive cyanide-insensitive manganese-containing enzyme (MnSOD) similar to that found in prokaryotes. In addition, a ferrienzyme (FeSOD) has been identified in bacteria that is also insensitive to cyanide. Amino acid sequence homologies indicate two families of superoxide dismutases. One of these is composed of the Cu,ZnSODs and the other of MnSODs and FeSODs. All these superoxide dismutases catalyze the same reaction (2H -H O2 -h OJ H2O2 -t- O2) and with comparable efficiency. 

Figure 8.8 Super Oxide Dismutase. (a) Disproportionation reaction catalyzed by super oxide dismutase (SOD) (b) cartoon display structure of homo-tetrameric MnSOD (manganese containing human mitochondrial) (pdb lnOj) illustrating two out of the four identical polypeptide chains (orange, yellow) and manganese ions (Mn +/ +) (purple) rendered as van der Waals spheres for complete clarity.

To diminish these threats, nature has created a family of metalloenzymes, the SODs. They catalyze the dismutation of superoxide to dioxygen and hydrogen peroxide (Eqs. (1) and (2)). They are differentiated by the redox-active metal copper (Cu/Zn SOD), manganese (MnSOD), iron (FeSOD), or nickel (NiSOD) superoxide dismutases and fall into three evolutionary families (Fig. 2) (10). The iron and manganese SODs are structurally similar and are found in prokaryotes and in the matrix of mitochondria (near the electron transport chain), respectively. Nickel containing SODs are known in some prokaryotes, whereas Cu/Zn are present in the cytosols of virtually all eukaryotic cells and have an independent evolutionary history. 

Mn(II) ions complexed by porphyrinato(2 ) ligands have shown catalytic superoxide anion dismutation. One SOD mimic, M40403, complexes Mn(II) via a macrocyclic ligand, 1,4,7,10,13-pentaazacyclopentadecane, containing added bis(cyclohexyl) and pyridyl functionalities. M40403 carries the systematic name [manganese(II) dichloro] 4R,9R, 14/s, 19/ )-3,10,13,20,26-pentaazatetracyclo[20.3. 1.0(4,9)0(14,19)]hexacosa-l(26),-22(23),24-triene ]. The molecule is shown in... 

To prevent membrane damage, the red cell has an armoury of antioxidants, notably a manganese or selenium containing enzyme called superoxide dismutase (SOD) and the sulfydryl compound glutathione (GSH), a tripeptide of y-glutamate, cysteine and glycine. 

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