Iron dismutase

These dismutases are still poorly characterized. Table 27 lists details of both iron- and manganese-containing enzymes. The manganese dismutases contain Mn ", and occur either as dimers or tetramers with subunits of molecular weight about 20 000. The Mn/subunit ratio varies from 0.5 through 1.0 to 2.0. The iron dismutases have subunits of 20 000 or 40 000 and an upper limit of one Fe" per subunit. It has been pointed out that most of the proteins are synthesized initially as precursors, which are between 2000 and 6000 larger in molecular weight than that of the mature protein. 

Copper is one of the twenty-seven elements known to be essential to humans (69—72) (see Mineral nutrients). The daily recommended requirement for humans is 2.5—5.0 mg (73). Copper is probably second only to iron as an oxidation catalyst and oxygen carrier in humans (74). It is present in many proteins, such as hemocyanin [9013-32-3] galactose oxidase [9028-79-9] ceruloplasmin [9031 -37-2] dopamine -hydroxylase, monoamine oxidase [9001-66-5] superoxide dismutase [9054-89-17, and phenolase (75,76). Copper aids in photosynthesis and other oxidative processes in plants. 

The hydroxyl radical plays two essentially different roles (a) as a reactant mediating the transformations of xenobiotics and (b) as a toxicant that damages DNA. They are important in a number of environments (1) in aquatic systems under irradiation, (2) in the troposphere, which is discussed later, and (3) in biological systems in the context of superoxide dismutase and the role of iron. Hydroxyl radicals in aqueous media can be generated by several mechanisms ... 

Touati D, M Jacques, B Tardat, L Bouchard, S Despied (1995) Lethal oxidative damage and mutagenesis are generated by iron Afur mutants of Escherichia coli protective role of superoxide dismutase. J Bacterial 111 2305-2314. 

Hassett DJ, HP Schweitzer, DE Ohman (1995) Pseudomonas aeruginosa sodA and sodB mutants defective in manganese- and iron-cofactored superoxide dismutase activity demonstrate the importance of the iron-cofactored form in aerobic metaholism. J Bacteriol 111 6330-6337. 

McCormick ML, GR Buettner, BE Britigan (1998) Endogenous superoxide dismutase levels regulate iron-dependent hydroxyl radical formation in Escherichia coli exposed to hydrogen peroxide. J Bacterial 180 622-625. 

Lipid peroxidation (see Fig. 17.2) is a chain reaction that can be attacked in many ways. The chain reaction can be inhibited by use of radical scavengers (chain termination). Initiation of the chain reaction can be blocked by either inhibiting synthesis. of reactive oxygen species (ROS) or by use of antioxidant enzymes like superoxide dismutase (SOD), complexes of SOD and catalase. Finally, agents that chelate iron can remove free iron and thus reduce Flaber-Weiss-mediated iron/oxygen injury. 

One last class of mononuclear non-haem iron enzyme that we have not yet considered, consists of the microbial superoxide dismutases with Fe(III) at their active site. The crystal structure of the E. coli enzyme shows a coordination geometry reminiscent of protocatechuate 3,4-dioxygenase, with four endogenous protein ligands, three His and one Asp residue, and one bound water molecule (Carlioz et ah, 1988). 

The mitochondrial dysfunctionality seen in manganese neurotoxicity might be related to the accumulation of reactive oxygen species (Verity, 1999). Mitochondrial Mn superoxide dismutase (MnSOD) is found to be low or absent in tumour cells and may act as a tumour suppressor. It is induced by inflammatory cytokines like TNF, presumably to protect host cells. In a rat model, iron-rich diets were found to decrease MnSOD activity, although a recent study reported that in rat epithelial cell cultures iron supplementation increased MnSOD protein levels and activity, but did not compromise the ability of inflammatory mediators like TNF to further increase the enzyme activity (Kuratko, 1999). 

FIGURE 5.11 EPR of an S = 5/2 system with pronounced rhombicity. The X-band spectra (V = 9.31 GHz) are from high-spin FeIH in Escherichia coli iron superoxide dismutase. The observed effective g-values correspond to T = 0.24 in the S = 5/2 rhombogram. 

V.W.F. Chan, M.J. Bjerrum, and C.F. Borders, Jr, Evidence that chemical modification of a positively charged residue at position 189 causes the loss of catalytic activity of iron-containing and manganese-containing superoxide dismutases. Arch. Biochem. Biophys. 279,195-201 (1990). 

M.E. Schinia, L. Maffey, D. Barra, F. Bossa, K. Puget, and A.M. Michelson, The primary structure of iron superoxide dismutase from Escherichia coli. FEBS Lett. 221, 87-90 (1987). 

D. Ringe, G.A. Petsko, F. Yamakura, K. Suzuki, and D. Ohmori, Structure of iron superoxide dismutase from Pseudomonas ovalis at 2.9. ANG. resolution. Proc. Natl. Acad. Sci. U.SA. 80, 3879-3883 (1983). 

W.C. Stallings, C. Bull, J.A. Fee, M.S. Lah, and M.L. Ludwig, Iron and manganese superoxide dismutases catalytic inferences from the structures. Current Communications in Cell Molecular Biology. 5, 193-211 (1992). 

A. Carlioz, M.L. Ludwig, W.C. Stallings, J.A. Fee, H.M. Steinman, and D. Touati, Iron superoxide dismutase. Nucleotide sequence of the gene from Escherichia coli K12 and correlations with crystal structures. J. Biol. Chem. 263, 1555-1562 (1988). 

B.L. Stoddard, P.L. Howell, D. Ringe, and G.A. Petsko, The 2.1. ANG. resolution structure of iron superoxide dismutase from Pseudomonas ovalis. Biochemisry. 29, 8885-8893 (1990). 

M.L. Ludwig, A.L. Metzger, K.A. Pattridge, and W.C. Stallings, The structure of iron superoxide dismutase from Pseudomonas ovalis complexed with the inhibitor azide. J. Mol. Biol. 219, 335-358 (1991). 

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