METABOLISM OF HARMOL AND TRANSPORT OF HARMOL CONJUGATES IN ISOLATED RAT HEPATOCYTES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 11  (5) , 433-440
Abstract
The conjugation of harmol and the disposition of harmol metabolites by isolated rat hepatocytes were investigated. Harmol sulfation was saturated at low concentrations and exhibited a maximum velocity of 1.2 .+-. 0.2 nmol/min per 106 hepatocytes. Glucuronidation of harmol proceeded with a Km of 17 .+-. 5.7 .mu.M and a maximal velocity of 2.1 .+-. 0.3 nmol/min per 106 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 .mu.M and Vmax of 1.8 .+-. 0.3 nmol/min per 106 hepatocytes. Harmol sulfate was taken up by 2 Michaelis-Menten processes, a high affinity process with a Km of 33 .+-. 8 .mu.M and a Vmax of 0.97 .+-. 0.2 nmol/min per 106 cells, and a low affinity process with a Km of 452 .+-. 71 .mu.M and Vmax of 25.2 .+-. 4.1/min per 106 hepatocytes. Harmol sulfate was released from hepatocytes by a process which did not exhibit saturation. Hepatocytes converted preformed harmol glucuronide to harmol sulfate.