Proteins binding cadmium

There is a protein, metallothionine, which is found in kidney and which binds cadmium and zinc very effectively. This may well be related to the bacterial protein. We see that biological systems have developed highly selective ways of countering the influence of poisonous metals. The protection involves the interaction between a selected protein and a given metal. We can now return to platinum chemistry. 

The binding of transcription factors to nucleotide sequences, which facilitates gene transcription, can be influenced by chemicals. For example, cadmium binds to a metal-binding protein factor, MFF-1, in place of zinc and so induces metallothionein synthesis. This, as it happens is a detoxication, as metallothionein binds cadmium. 

Metallothioneins are a unique and widely distributed group of proteins. They are characterized by their low molecular weight (—6000), high cysteinyl content, and the ability to bind substantial numbers of metal ions (43). The proteins bind copper and zinc, thereby providing a mobile pool as part of the normal metabolism of these elements, and offer protection from the invasion of inorganic forms of the toxic elements cadmium, lead, and mercury. In addition, other metals, such as iron and cobalt, can be induced to bind. XAS is ideally suited to probe the environment of these different metal atoms (see Fig. 1), and the structural interpretations obtained from an analysis of the EXAFS data obtained in several such studies are summarized in Table 1(44). Thus, in each case, the data are consistent with the primary coordination of the metal deriving from the cysteinyl residues. 

Jamba L, Nehru B, Bansal MP. 1997. Redox modulation of selenium binding proteins by cadmium exposures in mice. Mol Cell Biochem 177 169-175. 

Tables 63-6.5 list some of the causes that affect plasma calcium, magnesium, and phosphate. Increased plasma calcium concentration may occur when the xeno-biotic specifically targets calcium metabolism, behaves similarly to vitamin D, and causes hyperparathyroidism or renal disease. Lead and cadmium enter bone and inhibit bone growth, increase calcium release from bone, and inhibit renal tubular reabsorption of calcium salts lead inhibits the renal bioactivation of 25-hydroxy-cholecaliciferol (Sauk and Somerman 1991). In longer-term studies, increased plasma calcium may be associated with tumor burden. Because roughly half of circulating calcium is bound to plasma albumin, hypercalcemia can also arise from dehydration. Hypoparathyroidism, pancreatitis, and renal disease can reduce plasma calcium. Acidosis increases plasma-ionized calcium concentrations, whereas alkalosis causes a decrease due to the effects of pH in the ECF or on protein binding.

Wolkowski-Tyl, R. M., Strain and tissue differences in cadmium-binding protein in cadmium-treated mice. In Developmental Toxicology of Energy-related Pollutants D.O.E. Symposium Series, 1978, 47 568-585. 

After intravenous injection in experimental animals, cadmium in the blood is initially found mainly in the plasma, but later a shift takes place to r d blood cells, where the cadmium binds to proteins such as metallothionein and hemoglobin. Metallothionein is of great importance for the transport, excretion, and toxicity of cadmium. It was initially isolated firam equine r nal cortex and has a molecular weight of about 6000-7000. It can bind cadmium, zinc, and other metals owing to the presence of a large number of sulfhydryl gixrups and has been isolated from several tissues in man and animals. 

Cadmium is extremely toxic and accumulates in humans mainly in the kidneys and liver prolonged intake, even of very small amounts, leads to dysfunction of the kidneys. It acts by binding to the —SH group of cysteine residues in proteins and so inhibits SH enzymes. It can also inhibit the action of zinc enzymes by displacing the zinc. 

Rauser, W.E. (1984). Isolation and partial purification of cadmium-binding protein from roots of the grass Agrostis gigantea. Plant Physiology, 74, 1025-9. 

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. 

It is now established that cadmium, besides zinc, is accumulated in some native cysteine-rich proteins (e.g., metallothioneins) and the binding mode and sites in the protein are studied and largely understood.57 Also, the detection and study of native Cd-enzymes and Cd-substituted Zn-enzymes is just beginning at the time of writing (for a short survey see ref. 58). 

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