Abstract
Human blood esterases responsible for diacetylmorphine (DAM, heroin) metabolism were examined by means of an HPLC assay system for DAM, 6-monoacetylmorphine (MAM), and morphine. Four kinetically distinct enzymes capable of hydrolyzing DAM to MAM were observed in the plasma, erythrocyte (RBC) cytosol, and RBC membrane fractions of human blood. Under physiological conditions (pH 7.4, 37 degrees C), the Km (micromolar) and Vmax (micromolar per minute) values, respectively, for these enzymes were as follows: plasma, 200 and 210; RBC cytosol, 710 and 815; RBC membranes, 2000 and 748, and 38 and 80. For DAM blood concentrations less than or equal to 100 ng/mL, RBC associated esterases are responsible for the majority (76%) of DAM hydrolysis in blood.
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