Probing the biochemistry of toxic metals in the bloodstream

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Human activities, such as fossil fuel consumption and mining activities emit quantities of toxic metals that rival or exceed natural global emissions and they are projected to increase (e.g. coal consumption will increase by 1/5th over the next 25 years). This will be associated with an increased influx of inorganic pollutants into the human bloodstream. Despite much research, there exist considerable knowledge gaps with regard to our understanding of the biochemistry of toxic metals in the bloodstream. A better understanding of these processes, however, is urgently needed to establish the biochemical mechanisms which may link the exposure of humans - including children - to toxic metals with diseases and to develop strategies to efflux toxic metals from the body. The visualization of biochemical events that occur in the bloodstream, however, poses a major problem. Dr. Gailer's group has developed a methodology which allows to analyze blood plasma for proteins which contain a bound metal (e.g. iron, copper or zinc) and are therefore referred to as plasma metalloproteins. Since this methodology can simultaneously detect any toxic metals that are added to plasma, we can gain fundamentally new insight into biochemical processes by which toxic metals may adversely effect the metabolism of essential metals. In addition, it allows to study the effect of drugs (so-called chelating agents) which can be administered to intoxicated humans to increase the mobilization of a toxic metal from the body. The developed methodology will be systematically applied to probe the effect of toxic metals in plasma at the metalloprotein level and to study the efficacy of chelating agents. Novel metal-containing metabolites will be structurally characterized using an advanced spectroscopic technique (Canadian Light Source, Saskatoon). This approach is expected to provide exciting new insights into the toxicology of environmentally abundant toxic metals and metalloid compounds and is the prerequisite for the development of remedies against the chronic toxicity of metal/metalloids in humans. The proposed research thus represents an initiative to advance human health in the 21st century.