Copper lipid-soluble

Lipid-soluble food grade copper chlorophyll is manufactured similarly by extraction of adequate plant material, followed by replacement of magnesium by copper, and purihcation steps to remove carotenoids, waxes, sterols, oils, and other minor components that are co-extracted. Commercial copper chlorophylls may vary physically, ranging from viscous resins to fluid dilutions in edible oils as well as granulated forms and emulsions standardized with edible vegetable oil. Colors may vary... 

In seawater, the major chemical species of copper are Cu(OH)Cl and Cu(OH)2 and these account for about 65% of the total copper in seawater (Boyle 1979). The levels of copper hydroxide (Cu(OH)2) increase from about 18% of the total copper at pH 7.0 to 90% at pH 8.6 copper carbonate (CuC03) dropped from 30% at pH 7.0 to less than 0.1% at pH 8.6 (USEPA 1980). The dominant copper species in seawater over the entire ambient pH range are copper hydroxide, copper carbonate, and cupric ion (USEPA 1980). Bioavailability and toxicity of copper in marine ecosystems is promoted by oxine and other lipid soluble synthetic organic chelators (Bryan and Langston 1992). 

Ahsanullah, M. and Florence, T. M. (1984). Toxicity of copper to the marine amphiphod Allorchestes compressa in the presence of water- and lipid-soluble ligands, Marine Biol., 84, 41-45. 

Florence, T. M., Powell, H. K. J., Stauber, J. L. and Town, R. M. (1992). Toxicity of lipid-soluble copper(II) complexes to the marine diatom Nitzschia Closterium -amelioration by humic substances, Water Res., 26, 1187-1193. 

There are several such toxic agents that cause considerable medical, public and political concern. Two examples are discussed here the heavy metal ions (e.g. lead, mercury, copper, cadmium) and the fluorophosphonates. Heavy metal ions readily form complexes with organic compounds which are lipid soluble so that they readily enter cells, where the ions bind to amino acid groups in the active site of enzymes. These two types of inhibitors are discussed in Boxes 3.5 and 3.6. There is also concern that some chemicals in the environment, (e.g. those found in industrial effluents, rubbish tips and agricultural sprays), although present at very low levels, can react with enhanced reactivity groups in enzymes. Consequently, only minute amounts concentrations are effective inhibitors and therefore can be toxic. It is suggested that they are responsible for some non-specific or even specific diseases (e.g. breast tumours). 

If an aqueous sample is shaken with a volume of immiscible organic solvent, uncharged species tend to be extracted into the organic layer. This liquid-liquid extraction procedure has some applications in speciation studies. For example, organically associated copper species have been isolated by extracting water samples with chloroform, carbon tetrachloride (Slowey et al., 1967) or hexane. The lipid-soluble fraction of copper and other metals has been extracted from natural waters using solvent mixtures such as w-hexane, 10% butanol and w-octanol and 20% butanol in hexane (Stiff, 1971 Florence, 1982). The liquid-liquid extraction efficiencies are possibly low, due to... 

Therefore, PG is widely used in foods where lipid-soluble antioxidants such as BHA, BHT, and TBHQ are not suitable. PG is inappropriate for frying due to its poor stability at high temperatures. It decomposes at its melting point of 148°C (11, 12). Gallates can form undesirable, dark-colored complexes with iron and copper thus, they are sold as a mixture with metal chelators such as EDTA. Gallates also act synergistically with other antioxidants (11, 12). 

The lipid-soluble antioxidants present in the LDL particle are responsible for the LDL particle resistance to oxidation [3]. LDL copper-mediated oxidability in vitro, has been used by several researchers to evaluate oxidation resistance of LDL. LDL oxidation is evaluated by following in vitro copper-mediated oxidation of LDL [3,49]. Duration of the lag phase determines the resistance of LDL to oxidation and depends on the content of antioxidants in the LDL molecule. During the lag period, the alpha-tocopherol and other antioxidants are lost from LDLs. The length of the lag phase reflects the protective effects of chain-breaking antioxidants, especially alpha-tocopherol. When LDL particles, isolated from subjects who have consumed vitamin E supplements, or are enriched with vitamin E, the length of lag period is significantly increased [3]. 

The Cu-Zn-SOD-mimetic activity of Cu(II)(3,5-DIPS)2 and its lipid solubility were criteria used to select this complex in the initial attempt to study a copper complex as a radioprotectant. This complex was found to prevent death in 58% of the lethally irradiated (10 Gy, 0.4Gy/min) mice when they were thought to have been treated with 0.49 mmol/kg, 3 h before irradiation [505]. Subsequent studies revealed that this protection could be achieved with a much lower dose of complex suspended in a propyleneglycol-poly(vinyl alcohol)-saline vehicle. Treatment with 0.16 mmol/kg produced a 60% increase in survival in similarly irradiated and treated mice [506]. Most recent studies suggest that this radioprotectant effect may be achieved with a still further reduced dose of 0.04 mmol/kg and this lower dose appears to be as effective if given 3 h after irradiation as it is when given 3 h before irradiation. 

Subsequent research led to the discovery that p-aminosalicylic acid (PAS) was an active antitubercular agent, and it was suggested that the antitubercu-lar activity of this drug was due to its Cu(II) complex [526], which was prepared and found to be 10-times as active as PAS itself [527]. Studies of Cu(II)(4-aminosalicylate)2 also revealed that it was 30-times more lipid-soluble than PA [528, 529]. The enhanced activity of the copper complex was attributed to this increased lipid solubility, which facilitated penetration of the fatty outer membrane of Mycobacterium tuberculosis. 

In principle, ascorbic acid and its salts (sodinm or calcinm ascorbate) are water solnble antioxidants, not widely applicable for lipid systems but extensively nsed in beverages. In aqneons systems containing metals, ascorbic acid may also act as a prooxidant by reducing the metals that become active catalysts of oxidation in their lower valences. However, in the absence of added metals, ascorbic acid is an effective antioxidant at high concentrations. The action of ascorbic acid in lipid autoxidation is dependent on concentration, the presence of metal ions, and other antioxidants. It has been shown that ascorbates can protect plasma and LDL lipids from peroxidative damage, and it may inhibit the binding of copper ions to LDL. " In several countries, ascorbic pahnitate is used in fat containing foods due to its lipid solubility. However whether ascorbic palmitate exerts a better... 

A fourth complex connects site 1 to site 2. Thus, the first complex in the chain consists of the enzyme NADH dehydrogenase and a group of around five closely linked proteins that contain electron-rich iron-sulphur clusters. These are non-heme proteins vital to the flow of electrons through the chain. The second complex consists of the enzyme succinate dehydrogenase and its collection of iron-sulphur proteins. The third complex contains the hemoproteins cytochromes b and Cj, and one iron-sulphur protein. The final complex, the one that actually reduces oxygen to water, is called cytochrome oxidase and contains two heme groups (heme a and heme a ) and two copper centres. Ubiquinone, also known as coenzyme Q, is a lipid-soluble quinone which connects the first, second, and third complexes. Cytochrome c is the electron carrier hemoprotein that links the complexes of site 2 to cytochrome oxidase in site 3. 

Lipid-soluble metal complexes such as copper xanthates (from mineral flotation plants), copper 8-hydroxyquinolinate (agricultural fungicide) or alkyl-mercury compounds are particularly toxic forms of heavy metals because they diffuse rapidly through a biomembrane and carry both metal and ligand into the cell. ... 

The antimicrobial activity described here is only valid for 8-hydroxyquinoline and not for the seven other possible hydroxyquinolines which are widely inactive and do not, as does 8-hydroxyquinoline, chelate metal cations, e.g. copper, iron and zinc. Contrary to Oxine the corresponding chelation complexes, e.g. copper 8-hydroxyquinoline (Section 11.5) possess considerable lipid solubility enabling the complex to pass through the cell membrane and then to dissociate into the toxic 8-hydroxyquinoline. However, according to the findings of Block (1983)... 

Certain compounds are able to react with free radicals to form a stable compound which is harmless. Vitamin E is especially effective in this respect and its antioxidant activity is promoted by vitamin C, /3-carotene and certain other lipid-soluble antioxidants. On the other hand, iron and copper salts have a deleterious effect. The ability of )8-carotene to scavenge free radical intermediates is not related to its role as provitamin A but depends on the large number of double bonds in the molecule. 

Some tumour growth inhibition was observed for Cu(SOD) itself [83]. The demonstrated SOD-mimetic activity (albeit low) of copper complexes such as bis(isopropylsalicylato)copper(II), prompted a study of its antitumour effect, the reasoning being that this lipid-soluble analogue would have greater uptake in cells. The complex (Structure 63) is probably of the cupric acetate type ... 

An antioxidant can be described in simple terms as anything that can delay or prevent oxidation of a susceptible substrate. Our antioxidant system is complex, however, and consists of various intracellular and extracellular, endogenous and exogenous, and aqueous and lipid-soluble components that act in concert to prevent ROS formation (preventative antioxidants), destroy or inactivate ROS that are formed (scavenging and enzymatic antioxidants), and terminate chains of ROS-initiated peroxidation of biological substrates (chain-breaking antioxidants). In addition, metals and minerals (such as selenium, copper, and zinc) that are key components of antioxidant enzymes are often referred to as antioxidants. 

Figure 18.16 Hypothetical model for the metallobiology of AP in Alzheimer s disease. (From Bush, 2003. Copyright 2003, with permission from Elsevier.) The proposed sequence of events (1) concentration of iron and copper increase in the cortex with aging. There is an overproduction of APP and AP in an attempt to suppress cellular metal-ion levels. (2) Hyper-metallation of AP occurs which may facilitate H202 production. (3) Hyper-metallated AP reacts with H202 to generate oxidized and cross-linked forms, which are liberated from the membrane. (4) Soluble AP is released from the membrane and is precipitated by zinc which is released from the synaptic vesicles. Oxidized AP is the major component of the plaque deposits. (5) Oxidized AP initiates microglia activation. (6) H202 crosses cellular membranes to react with Cu and Fe, and generate hydroxyl radicals which oxidize a variety of proteins and lipids.

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