Xenobiotics protein binding

Plasma proteins are amphoteric molecules having both positive and negative charges that contribute to the balance of plasma ions and osmolality, particularly albumin. In cardiotoxicity, plasma protein patterns may be altered with increases of total protein, albumin, and acute phase proteins (e.g., myoglobin, C-reactive protein, and hbrinogen see Chapters 7 and 8). When proteins bind xenobiotics (or metabolites), their contributions to cation/anion balance may be altered. 

Lipophilic materials require intracellular carrier proteins to be optimally mobilized, just as they required transport proteins in the blood (Figure 10.3). Several intracellular carrier proteins that mobilize specific endogenous chemical have been characterized, although less is known of which proteins typically mobilize xenobiotics. Some of the cytosolic glutathione S-transferase proteins have been shown to noncatalytically bind xenobiotics and to be coordinately induced along with xenobiotic biotransformation enzymes and efflux transporters, suggesting that these proteins may function to mobilize xenobiotics. 

DNA binding activity of nuclear proteins to xenobiotic responsive element (XRE) was measured using EMSA as described previously 24),... 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

FIGURE 5.37 Janus faces of the biotransfbrmation of xenobiotics. On one hand metabolism leads to inactivation and elimination of xenobiotics, but on the other hand many metabolites are reactive and may cause deleterious effects by binding to DNA, proteins, and other macromolecules. 

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