Copper and iron proteins

Copper and Iron Proteins by Pulse Radiolysis Experiments. 

The concept of the photosynthetic and respiratory systems is that they are based on the rapid flow of electrons through a graded sequence of redox steps mediated by a continuous sequence of carriers [Change (27)]. Hemoproteins play an important role here, as do other "organic carriers like quinones, flavins, and copper and iron proteins. 

Elucidation of Electron- Transfer Pathways in Copper and Iron Proteins by Pulse Radiolysis Experiments... 

Copper and iron proteins participate in many of the same biological reactions ... 

R.B. King, ed. (1994) Encyclopedia of Inorganic Chemistry, Wiley, Chichester volumes 2 and 4 contain detailed reviews of copper and iron proteins, respectively. 

Ceruloplasmin is a protein for which many functions have been proposed - somewhat akin to Pirandello s Six Characters in Search of an Author, ceruloplasmin has long been a protein in search of a function. However, its importance in iron metabolism has been underlined by the observation of systemic iron loading in the tissues of patients with aceruloplasminaemia and other mutations in the ceruloplasmin gene. For further information on copper and iron interactions, see Chapter 12. 

In concluding this section, we stress again the novel dependence of the extracellular connective structures on chemistry, especially that of copper and iron using oxygen, and zinc proteins for hydrolysis, which did not and could not have taken place before more than one billion years ago. They arose mainly after the development of unicellular eukaryotes, and were dependent on additional environmental change. Even several external uses of calcium depend upon new oxidation of the side chains of proteins. 

NR is c/ s -1,4-polyisoprcnc, of molecular weight 200,000-500,000, but it also contains a small level of highly important non-rubber constituents. Of these, the most important are the proteins, sugars and fatty acids which are antioxidants and activators of cure. Trace elements present include potassium, manganese, phosphorus, copper and iron which can act as catalysts for oxidation. 

Iron and copper in wines may form complexes with other components to produce deposits or clouds in white wines. Iron clouds generally occur at a pH range from 2.9 to 3.6 and are often controlled by adding citric acid to the wines (2). Copper clouds appear in wines when high levels of copper and sulfur dioxide exist and are a combination of sediments, protein-tannin, copper-protein, and copper-sulfur complexes (169). Further, the browning rate of white wines increases in the presence of copper and iron (143). The results of this study indicate that iron increased the browning rate more than copper. 

It is not known at present if the nickel is coordinated directly to the protein, as in copper and iron-sulfur proteins, or to an organic cofactor, as in the molybdenum hydroxylases and hemoproteins. 

If our postulates are correct the most interesting feature of P-450 is the manner in which the protein has adjusted the coordination geometry of the iron and then provided near-neighbour reactive groups to take advantage of the activation generated by the curious coordination. Vallee and Williams (68) have observed this situation in zinc, copper and iron enzymes and referred to it as an entatic state of the protein. It is also apparent that some such adjustment of the coordination of cobalt occurs in the vitamin B12 dependent enzymes. As a final example we have looked at the absorption spectra of chlorophyll for its spectrum is in many respects very like that of a metal-porphyrin. This last note is intended to stress the features of chlorophyll chemistry which parallel those of P-450. 

Magaki S, Raghavan R, Mueller C, Oberg KC, Vinters HV, Kirsch WM. 2007. Iron, copper, and iron regulatory protein 2 in Alzheimer s disease and related dementias. Neurosci Lett 418 72-76. 

The significance of small amounts of metals to the Maillard reaction appears to have been first studied by Webb169 in 1935, in his work on the color of evaporated milk. The browning of lactose solutions at 49° was found to be positively catalyzed by copper and iron, but retarded by tin. Traces of cupric salts similarly accelerate the browning of amino acids or proteins with D-glucose in weakly alkaline solutions, but they have no ef-... 

Fig. 7. Cartoon depicting the functional and epistatic relationship between copper and iron uptake and trafficking in yeast. The handling of iron hy eukaryotic cells is ultimately dependent on a copper ferroxidase. In yeast, either copper deficiency or loss of function in any of the copper-handling proteins indicated in the cartoon causes an iron deficiency that is correctable readily by extranutritional copper but not by iron. Loss of function in FetSp or Ftrlp, however, is correctable by neither metal ion.

Fig. 14. Redox cycling in the uptake of copper and iron. The lower valent state species is substrate for uptake of copper and iron. The system in the yeast Saccharomyces cerevisiae is diagrammed. The Frel protein reduces environmental Cu " and Fe +. The cuprous ion is substrate for the copper permease, Ctrip. Fe + is substrate for Fet3p its oxidation to Fe + is an obligate step in iron uptake through Ftrlp. Exogenous ferric iron is not taken up by yeast cells unless it is cycled through the ferrireduction-ferrox-idation reactions catalyzed by Frelp and FetSp.

In the area of copper metabolism, four topics are covered bacterial copper transport reviewed by Huat Lu and Sohoz copper P-type ATPases reviewed by Voskoboinik, Camakaris, and Mercer copper chaperones reviewed by Stine Elam et al. and copper metaUoregulation of gene expression reviewed by Winge. An important related topic is the link between copper and iron metabolism. In this area, Kosman has reviewed the multicopper oxidase enzymes, such as FetSp and ceruloplasmin, which catalyze the conversion of iron(II) to iron(III) in preparation for its specific transport by partner transporter proteins. 

It is now widely agreed that both copper and iron are essential components 52-56). The metal content (11 nmoles/mg protein) and the iron to copper ratio (1.0) are well established for the bovine enzyme, whereas in yeast the reported metal contents are higher and more variable (5-15 nmoles of iron per milligram of protein) and the copper to iron ratio is greater than unity ( 1.5) (Table II) (44-4 > 48-52, 57-59). The iron is present as the unusual heme, heme A, with an apparently unique structure (Fig. 2) 60). The coordination environment of copper is far less clear, but the easy reducibility of copper seems to require a ligand envi-... 

Recent reviews on copper homeostasis in E. col and yeast are available. Copper and iron metabolism are often intertwined. For instance, mammalian iron metabohsm depends on the copper protein, ceruloplasmin, a ferroxidase that facilitates iron efflux from cells see Copper Proteins Oxidases) Several important human diseases, including Menkes disease and Wilson s disease, result from mutations in copper transport see Metal-related Diseases of Genetic Origin) ... 

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