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  • Title: Metabolism of harmol and transport of harmol conjugates in isolated rat hepatocytes.
    Author: Sundheimer DW, Brendel K.
    Journal: Drug Metab Dispos; 1983; 11(5):433-40. PubMed ID: 6138228.
    Abstract:
    The conjugation of harmol and the disposition of harmol metabolites by isolated rat hepatocytes were investigated. Harmol sulfation was saturated at very low concentrations and exhibited a maximum velocity of 1.2 +/- 0.2 nmol/min/10(6) hepatocytes. Glucuronidation of harmol proceeded with a Km of 17 +/- 5.7 microM and a maximal velocity of 2.1 +/- 0.3 nmol/min/10(6) hepatocytes. After synthesis, harmol glucuronide and harmol sulfate were distributed between cells and incubation media, and at equilibrium, a large concentration gradient between cells and media existed for both conjugates. Experiments with preformed metabolites indicated that hepatocytes removed harmol glucuronide from the incubation media by single Michaelis-Menten process with a Km of 384 +/- 63 microM and Vmax of 1.8 +/- 0.3 nmol/min/10(6) hepatocytes. Harmol sulfate was taken up by two Michaelis-Menten processes, a high affinity process with a Km of 33 +/- 8 microM and a Vmax of 0.97 +/- 0.2 nmol/min/10(6) cells and a low affinity process with a Km of 452 +/- 71 microM and Vmax of 25.2 +/- 4.1/min/10(6) hepatocytes. Harmol sulfate was released from hepatocytes by a process which did not exhibit saturation. Hepatocytes converted preformed harmol glucuronide to harmol sulfate.
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