Copper transport systems

Intracellular transport of metal ions has been a very well studied research area in the last few years. The most often-cited case of this transport involves copper transport in yeast by the copper metallochaperones 24, 25). Cu(I) enters the cytoplasm of yeast via copper transport receptors, and Cu(I) is bound by one of three transport proteins Lys7, Atxl, or Cox 17. Lys7 delivers copper to CuZn superoxide dismutase, Atxl delivers copper to ccc2 that activates an Fe(II) uptake system, and Cox 17 delivers copper to the mitochondria for the ultimate uptake into cytochrome c oxidase. A similar copper transport system has been reported in humans (26), and there may be a system in bacteria as well (27). Metal ion transport systems are known for iron, nickel, and manganese 24, 25, 28). However, no cytoplasmic Zn(II) transporters have been identified in... 

Since copper is an essential ion for the metabolism of cells, a chromosomal-based uptake system must exist. The cut system has been identified in . coli. Little is known about the system since only one of the genes has been sequenced cutE). The copB gene in Enterococcus that was previously sequenced has now been identified as a cut gene. The sequence of the copB gene reveals homology to P-type ATPases and may provide a clue to the mechanism of other chromosome-based copper transport systems. 

The copper concentrations of the kidneys, spleen, pancreas, and placenta of the diseased fetus were significantly higher than those from controls. Therefore, the gene mutation that occurs in the steely-hair syndrome may affect the copper transport system of organs other than the intestine. 

In Nature, microorganisms have developed copper transport systems to complete delivery of copper to target proteins [61]. Isolation of MCO enzymes produced in the native organism will best ensure that the holoenzyme has full complement of copper... 

NOTE Probably the most important junction of oxygen scavengers is, in reality, the ability to passivate boiler steel. In recognition of this, today most novel oxygen scavenger trials try to identify, not merely comparative oxygen reaction rates, but more importantly, the reduction in iron and copper transport rates through the boiler system. In other words, they seek to optimize the passivation of boiler surfaces and other system components. 

In microbes without a permeability barrier, or when the barrier fails, a mechanism must be in place to export metals from the cytoplasm. These active transport systems involve energy-dependent, membrane-bound efflux pumps that can be encoded by either chromosomal- or plasmid-borne genes. Active transport is the most well-studied metal resistance mechanism. Some of these include the ars operon for exporting arsenic from E. coli, the cad system for exporting cadmium from Staphylococcus aureus, and the cop operon for removing excess copper from Enterococcus hiraeP i9A0... 

Franke, S., Grass, G., Rensing, C., and Nies, D.H., Molecular analysis of the copper-transporting efflux system CusCFBA of Escherichia coli, J Bacteriol, 185 (13), 3804-3812, 2003. 

While unicellular fungi do not require metal transport systems, multi-cellular fungi and plants most certainly do, and we consider their transport in plants, and then consider how metal ions are sequestered in storage compartments before addressing their homeostasis. Once again, we consider in turn these processes for iron, copper and zinc. Since iron metabolism has been most intensively studied in S. cerevisiae, of all the fungi, we will focus our attention on iron homeostatic mechanisms, however, as the reader will see shortly, copper and zinc homeostasis have many similarities. 

The hemopexin heme transport system thus acts as an early warning system for cells by activating signaling pathways (including the N-terminal c-Jun kinase, kinases to release RbIA/NFkB family members for nuclear translocation) and transcription of the HO-1 and MT-1 genes. The details of this aspect of hemopexin function with redox-active copper as an initial event in the coordinated induction of HO-1 and MT-1 by heme-hemopexin have recently been reviewed (89) and are not presented in detail here. 

Like hemerythrin, hemocyanin is an oxygen transport non-heme-containing protein found in some arthropods and molluscs (104,105). In the 02-bound form, hemocyanin contains an antiferromagnetically coupled binuclear copper(II) system (106) ligated by histidine residues, with a sideways / 2-v2 V2 peroxo group bound to both Cu11 centers (104), which superseded the previous model (107). 

Transport and storage processes involving iron are by far the best understood, both for mammalian systems (transferrin and ferritin) and for microbes (the siderophores in iron transport). In addition, knowledge of the transport and storage of copper and zinc in mammalian systems is advancing steadily, although awareness of microbial transport systems in general is poor. 

The metals copper, chromium and cobalt also appear to be essential for growth for some, if not all, microorganisms.1218 Cobalt is an essential requirement for cobalamin-utilizing bacteria, but apart from being an alternative substrate for an Mg2+ transport system, there appears to be no highly specific transport system for Co2+. E. coli has a high affinity uptake system for cyanocobalamin, even though it does not require Bl2. Cobalamin may thus serve as a source of cobalt. 

In living systems that use metal ions in several places, transport of metal ions is an important process, for which efficient systems are in operation. Well-known examples are transferrin for iron transport in humans, albumin for copper transport, and ferritin for iron storage. In addition to these natural transporting proteins, nature makes use of other systems to remove excess of toxic metal ions. 

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