Superoxide dismutase metal transfer

Cu,Zn superoxide dismutase. Essentially, these observations support a stepwise one-electron model again. Interestingly, the oxidation state of copper does not change during the catalytic reaction, i.e. the sole kinetic role of the histidine coordinated metal center is to alter the electronic structures of the substrate and 02 in order to facilitate the electron transfer process between them. 

The most common metal encountered in electron transfer systems is iron, although copper and manganese play vital functions. Merely to emphasise the complexity of the catalysts that are used in biology, the structures of the active sites of ascorbate oxidase (Fig. 10-11) and superoxide dismutase (Fig. 10-12) are presented. It is clear that we have only just begun to understand the exact ways in which metal ions are used to control the reactivity of small molecules in biological systems. 

ACS = anunonium (-l-)-DlO-camphorsulfonate BSA = bovine serum albumin CD = circular dichroism CT = charge transfer hCCS = human copper chaperone for superoxide dismutase hSCAN = human soluble calcium-activated nucleotidase-1 LMCT = ligand-to-metal charge transfer METP = miniaturized electron transfer protein MECT = metal-ligand charge transfer ORD = optical rotatory dispersion SODs = superoxide dismutases tCCS = tomato copper chaperone for superoxide dismutase UTP = uracil triphosphate. 

Figure 1 An example of the way metallo-enzymes are under controlled formation through both controlled uptake (rejection) of a metal ion and controlled synthesis of all the proteins connected to its metabolism and functions. The example is that of iron. Iron is taken up via a molecular carrier by bacteria but by a carrier protein, transferrin, in higher organisms. Pumps transfer either free iron or transferrin into the cell where Fe + ions are reduced to Fe + ions. The Fe + ions form heme, aided by cobalamin (cobalt 2 controls) and a zinc enzyme for a-laevulinic acid (ALA) synthesis. Heme or free iron then goes into several metallo-enzymes. Free Fe + also forms a metallo-protein transcription factor, which sees to it that synthesis of all iron carriers, storage systems, metallo-proteins, and metallo-enzymes are in fixed amounts (homeostasis). There are also iron metallo-enzymes for protection including Fe SOD (superoxide dismutase). Adenosine triphosphate (ATP) and H+ gradients supply energy for all processes. See References 1 -3.

Once metals have been transported to their target tissue, they need to be distributed within the subcellular compartments where they are required, and need to be safely stored when they are in excess. Nearly 90% of Fe in plants is located in the chloroplasts, where it is required in the electron transfer chain, and in the synthesis of chlorophylls, haem, and Fe—S clusters. Fe, Cu, and Zn are also required in chloroplasts as cofactors for superoxide dismutases to protect against damage by reactive oxygen species during chloroplast development, and Cu is also required in other enzymes including the essential Cu protein plastocyanin. Pathways of intracellular metal transport in plant cells are illustrated in Fig. 8.10. Transport into the chloroplast is best characterised for Cu,... 

Hence, (ClgTPP)Fell (ClgTPP)Mnll facilitate the disproportionation of O2 -, which is equivalent to the function of the iron and manganese superoxide dismutase proteins. Whether the mechanism of Eq. (7-28) is relevant to those for the proteins is unknown, but the absence of electron transfer from their metal centers to O2 - is a reasonable expectation (as is radical-radical coupling of 02"-and the protein in the primary step of the disproportionation mechanism). 

A second belief of most biologists is that the superoxide dismutase proteins safely destroy O2 - via electron-transfer cycles at their transition-metal centers, for example. 

Copper occurs in almost all life forms and it plays a role at the active site of a large number of enzymes. Copper is the third most abundant transition metal in the human body after iron and zinc. Enzymes of copper include superoxide dismutase, tyrosinase, nitrite reductase and cytochrome c oxidase. Most copper proteins and enzymes have roles as electron transfer agents and in redox reactions, as Cu(II) and Cu(I) are accessible. 

The optical spectrum of iron superoxide dismutase is characterized by a broad band near 350 nm that is attributoi to a li nd-to-metal charge transfer band. The relatively high energy for this transition indicates that tyrosine is not a ligand to the Fe(lII). The EPR-spectrum is characteristically rhombic Azide and fluoride are inhibitors of the enzymatic activity. Intriguinly, cyanide does not affect the catalytic action. As in the case with the Cu ZHj enzymes, hydro n peroxide readily destroys the reactivity of iron SOD s, whereas manganese superoxide dismutases remain unaffected... 

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