Hydrogen sulfide poses a serious environmental health hazard to humans. Virtually all documented cases of acute sulfide poisoning have resulted from occupational exposure, and a least 72 occupations hazard a potential exposure to sulfide. Sulfide is toxic at the micromolar level due to reversible inhibition of cytochrome oxidase. The proper emergency treatment for acute sulfide poisoning is currently controversial. Use of sodium nitrite to induce methemoglobinemia or injection of exogenous heme compounds have been proposed as therapeutic measures, but the mechanism of detoxification is unknown. The beneficial action may be due to sulfide binding and sequestering of sulfide from cytochromes, or to an increased rate of sulfide oxidation catalyzed by ferric heme iron. The objectives of this study are to elucidate the biochemical mechanisms of heme reversal of sulfide toxicity and sulfide oxidation by heme compounds in order to provide a foundation for improving treatment of sulfide poisoning in humans. Published reports show the presence of sulfide oxidizing heme compounds in the coelomic fluid and epithelia of the marine worm Urechis caupo. The research proposed is a comparison of U. caupo heme compounds to the extremely sensitive human system and is divided into three sections; (I) biochemical characterization of heme compounds, (II) investigations of sulfide oxidase activity of enzymes and heme compounds, and (III) elucidation of the cellular mechanisms of sulfide detoxification. The methodology relies upon HPLC, NMR, spectrophotometry and autoradiography, X-ray microanalysis and standard light and electron microscopy with cytochemical staining. The research effort consistently involves undergraduate and graduate students in each of the three specific aims. Various subprojects will provide excellent opportunities for MBRS students to formulate hypotheses and realize their research goals while training on modern equipment. Publication and presentation of their results will encourage and enable them to successful pursue a career in the biomedical sciences.
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