Biomolecule

Information from the biomolecular level of organization is key to elucidating molecular mechanisms of toxicity, differences in sensitivity among individuals, and adaptation of populations to contamination. Understanding the molecular mode of toxic action also helps to predict how toxicant mixtures might affect exposed individuals. From a technological vantage, biochemical shifts are frequently used as evidence of toxicant exposure or effect.

Perhaps the best illustration would be the biomolecu-lar shifts involved in phase I and II reactions of organic contaminants. The levels of associated biomolecules can quickly increase during exposure. Type I reactions are mediated by enzymes that catalyze contaminant hydrolysis, reduction, or oxidation, producing more reactive metabolites. The metabolites might be more readily eliminated from the cell or participate in phase II detoxification reactions. The best-studied phase I system is cytochrome P-450 monooxygenase which transforms contaminants such as polycyclic aromatic hydrocarbons (PAHs), chlorinated hydrocarbons, polychlorinated biphenyls (PCBs), hydrocarbons, dioxins, and dibenzofur-ans. Although phase I transformations are intended to facilitate detoxification, some transformed contaminants are more toxic than the parent compounds or might be carcinogenetic. Phase II enzymes facilitate conjugation, that is, the addition of endogenous groups to contaminants or phase I metabolites which make the compounds more water soluble and readily eliminated.

Other biomolecules provide mechanistic insight and a foundation for biomarker technologies. Elevated concentrations of metallothioneins, cysteine-rich proteins that bind and sequester metals, are often employed as evidence of metal exposure. Also commonly used as biomarkers are stress proteins, proteins induced by chemical stressors that function to reduce protein damage (proteotoxicity). The recent surge in genetic technologies provides another suite of biomarkers. Changes in DNA, RNA, protein products, and cellular metabolites are used separately or together to reveal mechanisms of response or damage, and to document effects at the molecular level.

Molecular and ionic qualities of contaminants also influence the nature of exposure. An organism's exposure to the same amount of a contaminant under different conditions can result in different realized doses and consequences. For example, the free ion form of a dissolved metal is considered the most bioactive. Metals dissolved in water form complexes with ligands such as dissolved inorganic anions and natural organic compounds. Depending on the ionic composition of the waters, the same amount of dissolved metal will result in different concentrations of free ion and, consequently, concentrations of bioactive metal. Similarly, some organic contaminants are weak acids. If ingested with food, the capacity of such contaminants to pass through the gut wall and cause harm is dependent on the amount of unionized compound present. Unionized compounds are generally more amenable to passage across the gut wall than ionized compounds. Under different pH conditions, different amounts of such a weak acid would be unionized as can be easily estimated with the Henderson-Hasselbalch relationship:

^unionized

where /unionized is the fraction of the compound present that is unionized, and pKa the - log10 of the compound's ionization constant (Ka). Exploring the influence of molecular factors like the two just described is an active area of exposure research in ecotoxicology today.

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