Copper sequestration

Shiraishi N, Nishikimi M. 1998. Suppression of copper-induced cellular damage by copper sequestration with SlOOb protein. Arch Biochem Biophys 357(2) 225-230. 

Many reactions catalyzed by the addition of simple metal ions involve chelation of the metal. The familiar autocatalysis of the oxidation of oxalate by permanganate results from the chelation of the oxalate and Mn (III) from the permanganate. Oxidation of ascorbic acid [50-81-7] C HgO, is catalyzed by copper (12). The stabilization of preparations containing ascorbic acid by the addition of a chelant appears to be negative catalysis of the oxidation but results from the sequestration of the copper. Many such inhibitions are the result of sequestration. Catalysis by chelation of metal ions with a reactant is usually accomphshed by polarization of the molecule, faciUtation of electron transfer by the metal, or orientation of reactants. 

Phosphonates exhibit all the properties of polyphosphates, such as threshold effect, crystal distortion, and sequestration, but are superior in their effectiveness. They provide good chelates for calcium, magnesium, iron, and copper and are commonly used where iron fouling is a problem. Their sequestering properties are generally superior to other common chelants, such as EDTA and NTA. 

Aminotri(methylenephosphonic acid) [ATMP or AMP] is the least expensive phosphonate. It is a good, general-purpose, cost-effective scale inhibitor an effective chelant and the most thermally stable of all the common phosphonates. It is satisfactory up to at least 700 psia. However, if fed as a concentrate AIMP may easily form insoluble calcium phosphonate and it may also affect copper. ATMP has a sequestration value of 870 mg CaC03/g product at a pH level of 11 and for iron, a sequestration value of 150 mg Fe/g product at a pH level of 10. The pentasodium salt has a MW of 409. Examples include Dequest 2000/2006, Mayoquest 1230, Phos -2, Briquest 301-50A, Unihib 305, and Codex 8503. 

Phosphonobutane-l,2,4-tricarboxylic acid (PBTC) is the most expensive of the commonly used phosphonates. However it is excellent at providing calcium carbonate control under highly stressed operating conditions. It is most resistant to the problem of calcium phosphonate precipitation and, from an environmental position, has the lowest phosphorus content of the common phosphonates. The acid material has a MW of 270. PBTC has a sequestration value of 280 mg CaC03/g product at a pH level of 11. It is very stable and can operate under very high pH conditions. However, it may also attack copper. Examples include Bayhibit AM, Mayoquest 2100, Phos -9, and Codex 551. 

Metallothioneins are a group of small proteins (about 6.5 kDa), found in the cytosol of cells, particularly of liver, kidney, and intestine. They have a high content of cysteine and can bind copper, zinc, cadmium, and mercury. The SH groups of cysteine are involved in binding the metals. Acute intake (eg, by injection) of copper and of certain other metals increases the amount (induction) of these proteins in tissues, as does administration of certain hormones or cytokines. These proteins may function to store the above metals in a nontoxic form and are involved in their overall metaboHsm in the body. Sequestration of copper also diminishes the amount of this metal available to generate free radicals. 

Metallothionein was first discovered in 1957 as a cadmium-binding cysteine-rich protein (481). Since then the metallothionein proteins (MTs) have become a superfamily characterized as low molecular weight (6-7 kDa) and cysteine rich (20 residues) polypeptides. Mammalian MTs can be divided into three subgroups, MT-I, MT-II, and MT-III (482, 483, 491). The biological functions of MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis, and regulation of the biosynthesis and activity of zinc metalloproteins. 

Phosphates have the ability to combine with metal ions, such as calcium, magnesium, iron, and copper, and so render the metals nonactive. Calcium and magnesium arc primarily responsible for the hardness of water. The addition of tripolyphosphate or hexametaphosphale will hind these elements and produce soft water. In a similar manner, sequestration is used to soften the skins of fruits and vegetables for faster cooking, and to increase the extraction and recovery of pectin in fruit. Calcium pectinates, which are... 

Chelating agents or sequestrants remove metallic ions, especially copper and iron, that are powerful prooxidants. Citric acid is widely used for this purpose. Amino acids and ethylene diamine tetraacetic acid (EDTA) are other examples of chelating agents. 

Copper ion homeostasis in prokaryotes involves Cu ion efflux and sequestration. The proteins involved in these processes are regulated in their biosynthesis by the cellular Cu ion status. The best studied bacterial Cu metalloregulation system is found in the gram-positive bacterium Enterococcus hirae. Cellular Cu levels in this bacterium control the expression of two P-type ATPases critical for Cu homeostasis (Odermatt and Solioz, 1995). The CopA ATPase functions in Cu ion uptake, whereas the CopB ATPase is a Cu(I) efflux pump (Solioz and Odermatt, 1995). The biosynthesis of both ATPases is regulated by a Cu-responsive transcription factor, CopY (Harrison et al., 2000). In low ambient Cu levels Cop Y represses transcription of the two ATPase genes. On exposure to Cu(I), CopY dissociates from promoter/operator sites on DNA with a for Cu of 20 jlM (Strausak and Solioz, 1997). Transcription of copA and copB proceeds after dissociation of CuCopY. The only other metal ions that induce CopY dissociation from DNA in vitro are Ag(I) and Cd(II), although the in vivo activation of copA and copB is specihc to Cu salts. The CuCopY complex is dimeric with two Cu(I) ions binding per monomer (C. T. Dameron, personal communication). The structural basis for the Cu-induced dissociation of CopY is unknown. Curiously, CopY is also activated in Cu-dehcient cells, but the mechanism is distinct from the described Cu-induced dissociation from DNA (Wunderh-Ye and Solioz, 1999). 

Fig. 1. Schematic overview of copper trafficking and homeostasis inside the yeast cell. The actions of Mad and Ace 1, copper-dependent metalloregulatory transcription factors, control the production of copper import [copper transporter (Ctr) and reductase (Fre)] and detoxification/sequestration [metallothionein (MT)] machineries, respectively. Three chaperone-mediated delivery pathways are shown. Atxl shuttles Cu(I) to the secretory pathway P-type ATPase Ccc2 (right). CCS delivers Cu(I) to the cytoplasmic enzyme copper-zinc superoxide dismutase (SOD) (left). Coxl7 shuttles Cu(I) to cytochrome c oxidase (CCO) in the mitochondria (bottom). Mitochondrial proteins Scol and Sco2 may also play a role in copper delivery to the CuA and CuB sites of CCO. Copper metabolism and iron metabolism are linked through the actions of Fet3, a copper-containing ferroxidase required to bring iron into the cell (lower right) (see text).

Blend of sequestrants. Exceptionally high chelating values of iron and copper over a wide pH range. Can be used in diverse processes such as dyeing under acidic conditions or bleaching in an alkaline medium. 

Four major MT isoforms, MT-1, MT-2, MT-3, and MT-4, have been identified in mammals. The most widely expressed isoforms in mammals, MT-1 and MT-2, are rapidly induced in the liver by a wide range of metals, drugs, and inflammatory mediators. In the gut and pancreas, MT responds mainly to Zn status. A brain isoform, MT-3, has a specific neuronal growth inhibitory activity, while MT-1 and MT-2 have more diverse functions related to their thiolate cluster structure. These include involvement in Zn homeostasis, protection against heavy metal (especially Cd) and oxidant damage, and metabolic regulation via Zn donation, sequestration, and/or redox control. A possible role for MT-4 is related to copper requirements in epithelial differentiating tissues. 

Fraser, D. C. (1961). Organic sequestration of copper. Econ. Geol. 56, 1063-1078. 

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