Copper complexes albumin

Labile proteins. These include proteins such as transferrin (which complexes iron, as discussed previously) and albumin (which complexes copper, zinc, and other metals). 

A computer study has identified the critical chemical feature required in an AI agent to exploit serum albumin bound copper. Although the mechanism of action of copper complexes is unknown, stimulation of superoxide dismutase has been proposed as a contributing factor. ... 

Many, perhaps all, proteins have some degree of copper-complexing property. Of the serum proteins, albumin and transferrin have known copper-binding properties. When, however, copper is added to serum in excess of a 1 1 molar ratio in respect to albumin, then, in addition to albumin and transferrin, several other globulins will also bind some copper. 

Continuous microdetermination of protein with a Sephadex-Cu detection column has been described (G19). Radioactive copper is added to the plasma and the free Cu and the protein-bound isotope are separated at an alkaline pH by filtration through Sephadex. The free copper complexes with the hydrophilic gel and remains in the column. As little as 0.13 ng albumin in a volume of 1 ml may be determined. The main drawback of the method is the short life of the Cu isotope. 

A remarkable increase in SOD-mimetic activity was found in a comparison of synovial fluid from rheumatoid arthritis and osteoarthritic patients with normal control values [613]. The increase in SOD-mimetic activity correlated with increased rheumatoid disease activity and increasing progression of disease severity. There was also a good correlation between SOD-mimetic activity and C-reactive protein in synovial fluid from patients with rheumatoid arthritis. This SOD-mimetic activity may be attributed to either an elaboration of ceruloplasmin by synovial cells [614] or the liver along with copper albumin and amino-acid copper complexes which, in part, accounts for the established increase in synovial fluid copper and ceruloplasmin in rheumatoid arthritis [30] and it is well known that ceruloplasmin [102, 489, 615] as well as amino-acid and other small-molecular-weight copper complexes have SOD-mimetic activity [287-295, 327]. 

Complexes of metal + ligand + protein or DNA can also catalyze the Diels Alder cycloaddition or oxidations with hydrogen peroxide. Copper complexes bound to DNA catalyzed the Diels-Alder cycloaddition with up to 99% ee [15, 16], Cu(phthalocyanine) complexed to serum albumin also catalyzed the enantioselective (98% ee) Diels-Alder reaction, but only with very high catalyst loading (10 mol%) and only with pyridine-bearing dienophiles (presumably to complex the copper) [17]. Achiral Cr(III) complexes or Mn(Schiff-base) complexes inserted into the active site of apomyoglobin variants catalyzed the sulfoxidation of thio-anisole with up to 13 and 51% ee, respectively [18, 19]. A copper phenanthroline complex attached to the adipocyte lipid-binding protein catalyzed the enantioselective hydrolysis of esters and amides [20]. 

Fig. 14. Electron paramagnetic resonance spectra of low molecular mass copper complexes in the presence and in the absence of bovine serum albumin (BSA). All four copper concentrations are identical. Cu-EDTA served as standard. Cu flonazolac) displays no EPR-signal due the antiferromagnetic coupling of the two copper-centers. After addition of BSA, a signal of the biuret-type is obtained, indicating that the original complex was disrupted. A similar signal is seen after addition of CuSO, to BSA...

Concerning the catalytic superoxide dismutase activity of low molecular mass copper complexes, some general comments are neccessary. Firstly, it should be emphasized, that apart from the inactive Cu-penicillamine, all complexes described above do not survive high concentrations of biological chelators in aqueous solutions. For example, bovine serum albumine is able to remove most of the copper from these complexes (Fig. 14). 

The availability of copper in the body is somewhat different from that of iron. Copper in the Mood serum is bound in caeruloplasmin, Excessive dietary copper is predominately carried by serum albumin. Serum albumin copper is in the equilibrium with low molecular mass complexes of amino acids or small peptides. Unfortunately, the concentration of such complexes is below the detection limit. Regardless of the... 

Plasma copper exists in two forms 5% is loosely bound to albumin, and the remainder exists in the form of copper complexes. Copper forms ionic bonds with either an imidazole or a carboxyl group of the amino acid of albumin. Loosely bound copper reacts readily with dithiocarbamate, and therefore has been called the directly reacting copper. It is generally assumed but not established that the albumin that binds this copper plays an important role in transporting copper in the blood. 

Reetz and Jiao demonstrated the use of phthalocyanine-copper complex (267) in combination with a number of serum albumins as protein hosts in enantioselective Diels-Alder reactions of cyclopentadiene with azachalcones (Scheme 17.60) [86]. The combination of achiral Lewis acid (267) and bovine serum albumin as chiral host was determined to be optimal, giving the desired cycloadducts in good to excellent selectivities. Human, porcine, and sheep serum albumins also gave significant enantioselectivity, while rabbit and chicken-egg serum albumins resulted in nearly racemic cycloadduct. 

As with all antiarthritic drugs, the situation is not clear. Biochemical effects of copper are general, and no one target, such as a particular protein, is recognizable. The copper complexes are presumably a means of further increasing the copper content, because the species are expected to be rather labile. The introduction of exogenous copper will also affect thiol content and redox state of the cell, and some biochemical responses listed above may be a consequence of this altered state. Besides ceruloplasmin and albumin, major binding sites of Cu(II) are histidine and cysteine [94, 95] and some possibilities for the mechanism of action have been summarized [64]. 

Chromium has proved effective in counteracting the deleterious effects of cadmium in rats and of vanadium in chickens. High mortality rates and testicular atrophy occurred in rats subjected to an intraperitoneal injection of cadmium salts however, pretreatment with chromium ameliorated these effects (Stacey et al. 1983). The Cr-Cd relationship is not simple. In some cases, cadmium is known to suppress adverse effects induced in Chinese hamster (Cricetus spp.) ovary cells by Cr (Shimada et al. 1998). In southwestern Sweden, there was an 80% decline in chromium burdens in liver of the moose (Alces alces) between 1982 and 1992 from 0.21 to 0.07 mg Cr/kg FW (Frank et al. 1994). During this same period in this locale, moose experienced an unknown disease caused by a secondary copper deficiency due to elevated molybdenum levels as well as chromium deficiency and trace element imbalance (Frank et al. 1994). In chickens (Gallus sp.), 10 mg/kg of dietary chromium counteracted adverse effects on albumin metabolism and egg shell quality induced by 10 mg/kg of vanadium salts (Jensen and Maurice 1980). Additional research on the beneficial aspects of chromium in living resources appears warranted, especially where the organism is subjected to complex mixtures containing chromium and other potentially toxic heavy metals. 

Many copper(II) complexes, including Cu(DIPS)2 (DIPS = diisopro-pylsalicylate), Cu(salicylate)2, and Cu(Gly-His-Lys), are also active in superoxide dismutation (437, 438), but their use in vivo is limited by dissociation of Cu(II) and binding to natural ligands such as albumin (439). In contrast, the activity of Fe-93 is not affected by albumin (439, 440). 

Ortmans I, Moucheron C, Kirsch-De Mesmaeker A (1998) Ru(ll) polypyridine complexes with a high oxidation power. Comparison between their photoelectrochemisty with transparent SnC>2 and their photochemistry with desoxyribonucleic acids. Coord Chem Rev 168 233-271 Ozawa T, Ueda J, Flanaki A (1993) Copper(ll)-albumin complex can activate hydrogen peroxide in the presence of biological reductants first ESR evidence for the formation of hydroxyl radical. Biochem Mol Biol Int 29 247-253... 

The disturbance of copper excretion, primarily due to a defect in the billiary excretion, is consistent with the biochemical findings in patients with Wilson disease. Urinary copper excretion is increased owing to total body overload of copper. Renal dysfunction includes albuminuria and renal rickets. Incorporation of copper in ceruloplasmin is impaired. Thus, there is a greater proportion of copper bound to albumin and amino acid complexes in the serum. But the overall copper concentration in serum is low. Ceruloplasmin is a multicopper oxidase see Copper Proteins Oxidases) that... 

It is noteworthy that addition of another ligand (which can be histidine or cysteine) to carnosine complexes cause increased stability [30]. Addition of albumin leads to the similar effect [28], thus carnosine can effectively compete with albumin for copper or zinc ions [29],... 

Much of the copper in the plasma (60-95%) is bound to ceruloplasmin. The complex of copper and cenjloplasmir is assembled and secreted by the liver. A small fraction of plasma copper, under 7%, is weakly bound to albumin and to free amino acids, especially histidine, threonine, and glutamine. The copper bound to serum albumin is associated with a histidine residue near the amino terminus of the protein. The copper in red blood cells is bound to superoxide dismutase. 

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