Electron-transfer enzymes, role transition metals

Mechanistically, it was first proposed that the enzyme—metal—substrate (EMS) complex involved first-sphere coordination of substrate to enzyme-bound metal ion. For transition metal ions, 3d orbitals were suggested to facilitate catalysis by promoting delocalization of electrons in the substrate, thereby aiding bond lengthening and breakage, especially for proteases catalyzing peptide bond cleavage . For phosphate transfer enzymes, a transition between rr-levels in the donor-acceptor (substrate-metal) was proposed as the mechanistic role for metal in catalysis . 

The many redox reactions that take place within a cell make use of metalloproteins with a wide range of electron transfer potentials. To name just a few of their functions, these proteins play key roles in respiration, photosynthesis, and nitrogen fixation. Some of them simply shuttle electrons to or from enzymes that require electron transfer as part of their catalytic activity. In many other cases, a complex enzyme may incorporate its own electron transfer centers. There are three general categories of transition metal redox centers cytochromes, blue copper proteins, and iron-sulfur proteins. 

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. 

Electron-transfer (ET) reactions play a central role in all biological systems ranging from energy conversion processes (e.g., photosynthesis and respiration) to the wide diversity of chemical transformations catalyzed by different enzymes (1). In the former, cascades of electron transport take place in the cells where multicentered macromolecules are found, often residing in membranes. The active centers of these proteins often contain transition metal ions [e.g., iron, molybdenum, manganese, and copper ions] or cofactors as nicotinamide adenine dinucleotide (NAD) and flavins. The question of evolutionary selection of specific structural elements in proteins performing ET processes is still a topic of considerable interest and discussion. Moreover, one key question is whether such stmctural elements are simply of physical nature (e.g., separation distance between redox partners) or of chemical nature (i.e., providing ET pathways that may enhance or reduce reaction rates). 

The ability of transition metals to bind and activate organic molecules, and to release the transformed organic product with turnover, forms the basis of the vast catalytic chemistry of transition metal complexes. In addition, metal atoms play a key role at the catalytic center of many enzymes. For example, metalloenzymes play key roles in hydrolysis, oxidation, reduction, electron-transfer chemistry, and many other remarkable processes such as nitrogen fixation. The long-term development of synthetic polymers that perform catalytic chemistry in a manner analogous to enzymes, is a goal of profound interest. 

Metal ion assisted electron transfer reactions are important when considering the roles of sequesterants and enzymes in antioxidant protection (8). Compounds like ethylenediaminetetraacetic acid (EDTA), phytic acid, and polyphenols can sequester transition metal ions and thereby inhibit oxidation. Binding the metal ions essentially prevents them from regenerating hydroxy radicals through the Fenton reaction. 

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