Metal ions excretion

In a simplified model, the metal ions equilibrate on the outside of the cell with biologically produced and excreted ligands l 2 or ligands on the cell surface L3 these reactions are followed by a slow transport step to the inside of the cell. In the cell, the metal ions may be used in biochemical processes or become trapped in inactive forms as a detoxification mechanism. (After Williams, 1983) (cf. Fig. 4.15a). (From Sigg, 1987)... 

It acts as a chelating agent which helps in elimination of heavy metal ions by forming stable soluble complexes which can be easily excreted by the kidneys. 

Injection of calcium disodium EDTA does not affect blood calcium levels but heavy metal ions in the body have a higher affinity for EDTA than does calcium, and hence these metals readily exchange in vivo to form soluble EDT A-heavy-metal complexes that are excreted in the urine. Because of its poor absorption from the alimentary tract, calcium disodium EDTA is usually injected intramuscularly or intravenously. These considerations led to its being used, initially in 195270), to treat lead encephalopathy. 

To characterize the kinetic stabilities of complexes, the rate constants should be used, determined for the exchange reactions occurring between the complexes and endogenous metal ions (e.g. Cu2+ and Zn2+). Similarly to the equilibrium plasma models, the development of a kinetic model is needed for a better understanding of the relation between the extent of in vivo dissociation and the parameters characterizing the rates of dissociation, the rates of distribution in the extracellular space and the rates of excretion of the Gd3+ complexes. 

The slow release of manganese(II) from Mn-DPDP alters the tissue distribution of the metal ion. Free manganese ion is not cleared by the kidneys, but 43 % of an injected dose of Mn-DPDP in rats was excreted renally as either Mn-DPDP or other metabolites [18]. In addition, less cardiac accumulation of man-ganese(II) was seen with Mn-DPDP than MnCl2, leading to reduced cardiotoxi-city for the complex [25,26, 50, 51]. The bulk of the remaining manganese(II)... 

The metallothionines, for example, take care of transport and excretion of metal ions such as cadmium, and excesses of zinc and copper. A complete crystal structure of a metallothionine has been published. The protein structure contains seven metal ions coordinated by 20 cysteine residues in two regions of the protein. 

Endogenous substances other than metallothionein may be involved in minimizing the effects of heavy metals and excreting them from the body. Hepatic (liver) glutathione, discussed as a phase II conjugating agent in Section 7.4, plays a role in the excretion of several metals in bile. These include the essential metals copper and zinc toxic cadmium, mercury(II), and lead(II) ions and organometallic methyl mercury. 

Fig. 3.3 During load the Hey metabolic enzymes are decreased. This causes increase in Hey that chelates the metal ions, creating apoenzymes. Metal-Hcy is excreted from the cell. The treatment with copper-dependent ceruloplasmin mitigates the Hcy-dependent decrease in intracellular met-...

There are major challenges to be tackled relating to the chemical and biochemical mechanisms of action of organometallic complexes, for example involving the mechanism of displacement and release of coordinated arenes and cyclopentadienyl ligands which can expose several reactive coordination positions on a metal ion. Also the metabolism of coordinated arene and Cp ligands (e.g. modification by P450 enzymes in the liver) may have a major effect on the biodistribution and excretion of complexes. 

Further, compartmentalization allows cells to control the import of nutrients and the export of products that manipulate the environment, or excrete waste. These include siderophores that enhance uptake of metal ions, quorum-sensing molecules that inform cells of the presence of others of their kind, molecules that form biofilms that allow attachment to surfaces and protection from mechanical and chemical stress, and toxins that inhibit the growth of competitors. 

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