Albumin metals

The chemical form of a metal that accumulates in the kidney may vary among the metals. However, the ionic form of a metal is normally much more potent as a nephrotoxicant than the elemental form. Once in the body, metal ions interact with numerous molecules (albumin, metal-binding proteins, glutathione, amino acids, etc.) and move around the body primarily as reversible complexes. Unfortunately, little information is available on the chemical form of most metals that actually enters proximal tubular cells and additional research is needed in this area. 

Hormone response elements (for steroids, T3, retinoic acid, peptides, etc) act as—or in conjunction with— enhancers or silencers (Chapter 43). Other processes that enhance or silence gene expression—such as the response to heat shock, heavy metals (Cd and Zn +), and some toxic chemicals (eg, dioxin)—are mediated through specific regulatory elements. Tissue-specific expression of genes (eg, the albumin gene in liver, the hemoglobin gene in reticulocytes) is also mediated by specific DNA sequences. 

Albumin (various ligands, including bilirubin, free fatty acids, ions [Ca +], metals [eg, Cu, Zn ], metheme, steroids, other hormones, and a variety of drugs... 

Copper is an essential trace element. It is required in the diet because it is the metal cofactor for a variety of enzymes (see Table 50—5). Copper accepts and donates electrons and is involved in reactions involving dismu-tation, hydroxylation, and oxygenation. However, excess copper can cause problems because it can oxidize proteins and hpids, bind to nucleic acids, and enhance the production of free radicals. It is thus important to have mechanisms that will maintain the amount of copper in the body within normal hmits. The body of the normal adult contains about 100 mg of copper, located mostly in bone, liver, kidney, and muscle. The daily intake of copper is about 2—A mg, with about 50% being absorbed in the stomach and upper small intestine and the remainder excreted in the feces. Copper is carried to the liver bound to albumin, taken up by liver cells, and part of it is excreted in the bile. Copper also leaves the liver attached to ceruloplasmin, which is synthesized in that organ. 

Caeruloplasmin (Cp) is an acute phase glycoprotein with a copper transport function. At least 90% of total plasma copper is bound to Cp with the remaining 10% associated with albumin, histidine and small peptides. Lipid peroxidation requires the presence of trace amounts of transition metals and the copper-containing active site of Cp endows it with antioxidant capacity... 

Patwardhan, A.V. and Ataai, M.M., Site accessibility and the pH dependence of the saturation capacity of a highly cross-linked matrix. Immobilized metal affinity chromatography of bovine serum albumin on Chelating Superose, /. Chromatogr. A, 767, 11, 1997. 

Protective Colloids. Another approach in preparing and stabilizing metal colloids is by adsorption of macromolecules on their surfaces. A wide variety of materials have been used including gummy gelatinous liquids,(J 0) albumin,(27) Icelandic moss,(28) latex,(22) polyvinylpyrrolidone, (29) antibodies, ( 30 ) carbowax 20M, ( 31 ) polyvinylpyridine, (31 ) and various polymer-water/oil-water mixtures.( 2) These studies clearly indicate that "steric stabilization of metal colloids is also important (along with electronic stabilization).(33)... 

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. 

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