title: Metabolism of harmol and transport of harmol conjugates in isolated rat hepatocytes.
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.
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D005965:Glucuronates / Q000378:metabolism; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism*; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D013997:Time Factors
chemical_list: D000470:Alkaloids; D005965:Glucuronates; D007461:Iodoacetates; D013431:Sulfates; D012402:Rotenone; C001326:harmol; D006247:Harmine; D019807:Iodoacetic Acid