Models metal detoxification

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)... 

Most of the work on the individual tolerance concept has focused on organic chemicals. One of the reasons may be that for metals a CBR on a whole body basis has only limited applicability. Due to compartmentalization of metals in the body and the presence of regulation and detoxification mechanisms, it is unlikely that the total body residue is simply related to toxicity (see, e.g., Lock and Janssen 2001 Vijver et al. 2004). The biotic ligand models (BLMs) assume a critical level of metal accumulation at the biotic ligand and do not include a time aspect, although more TD-like approaches have been suggested (Paquin et al. 2002b). 

An additional feature in Fig. 2 worth noting is the amino-terminal 160 amino acids of mercuric reductase that lacked a fixed position in the crystal and therefore were not part of the solved structure. These contain the sequence that is homologous to MerP and postulated to be a mercurybinding domain. This region is drawn in Fig. 2 as an extension from the protein perhaps it functions like a baseball mitt that catches Hg from the membrane transport proteins and delivers Hg " to the carboxyl-terminal catalytic binding site, so that, as in the bucket brigade model above, Hg " is never found free within the cell. Mutant strains with the transport system but lacking the MerA detoxification enzyme are hypersensitive to mercury salts, as they accumulate Hg " but cannot get rid of it. After reduction by NADH (via FAD and the active site cysteine pair), metallic Hg is released... 

The specific mechanisms by which individual dietary components can alter the cancer process remain poorly understood. However, mechanisms underlying the carcinogenesis process are understood sufficiently so that model systems to evaluate the ability of a specific compound to inhibit or promote processes that may prevent or delay cancer development can be predicted. Phytochemcials can act at a variety of sites relevant to the development of the cancer cells. They may inhibit carcinogen activation, induce hepatic detoxification pathways, exert antioxidant effects/metal chelation properties, enhance immune response, induce apoptosis, and alter hormonal environment. 

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