HEMOGLOBIN, MYOGLOBIN, ALCOHOL, AND HEART DISEASE

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The project's long-term objectives are an understanding of the in vivo significance and the mechanisms of hemoglobin- and myoglobin-catalyzed monooxygenase-like reactions. One specific aim is to determine by in vitro studies whether hemoglobin and myoglobin catalyze or otherwise participate in monooxygenase- like alcohol oxidations; the results, if positive, might have a direct bearing on the physiological mechanism for ethanol abuse- induced heart disease. A second specific aim is to determine whether protein participation in catalysis is the reason that hemoglobin shows two different kinetic constants (KM's) for monooxygenase-like ring hydroxylation and demethylation of the same substance N-methyl aniline. The first aim will be accomplished by in vitro catalysis assays involving hemoglobin or myoglobin and ethanol or methanal under monooxygenase conditions. A nonenzymatic spectrophotometric assay for acetaldehyde (the product of ethanol oxidation) will be refined for use in the assays. Both extent of reaction and also the degree to which the hemoglobin or myoglobin survives the reaction unchanged will be determined. The second aim will be accomplished by in vitro kinetics experiments involving N-methyl aniline oxidation under monooxygenase conditions. Myoglobin will be used as a single-site catalyst, and heme oligopeptides and water-soluble hemes will be used as catalysts that possess either minimal or no protein components. The results will be compared with the results from hemoglobin-catalyzed reactions.