Metabolism of dihalomethanes to formaldehyde and inorganic halide. I. In vitro studies.

Metabolism of dihalomethanes by rat liver cytosol fractions yielded formaldehyde and inorganic halide as products. Loss of metabolic activity resulting from dialysis of the cytosol was restored with glutathione. Cysteine could not substitute for GSH. No other cofactor was found to be required for activity. The optimum conditions for this biotransformation with respect to time, temperature, protein concentration, and pH were determined. Rates of metabolism of dihalomethanes showed the following order: CH2i2 greater than CH2Br2 congruent to CH2BrCi greater than CH2Ci2. Administration of the enzyme inducer, phenobarbital, to rats did not alter this metabolic pathway nor did repeated administration of CH2Br2 or CH2Ci2 change the rate of metabolism. The enzyme catalyzing this reaction was localized in the liver. Compounds known to serve as substrates for various GSH transferases inhibited the reaction as did those capable of interacting with sulfhydryl groups.