title: Mitochondrial ATPase: a target for paracetamol-induced hepatotoxicity.
abstract: We examined the effect of paracetamol treatment (650 mg/kg) on the function of ATPase from rat hepatic mitochondria. The drug treatment caused an overall 35% decrease in ATPase activity, with a complete loss of the high affinity component as determined by substrate kinetic studies. The Km for the intermediate and low affinity components decreased by about 30% without change in Vmax, which may represent a compensatory mechanism. The drug treatment also resulted in a dramatic decrease in the phase transition temperature by about 19 degrees C without affecting the energies of activation of the enzyme. Mitochondrial total phospholipid content increased significantly with a reciprocal decrease in the cholesterol content. The total phospholipid/cholesterol molar ration increased by 50% after paracetamol treatment. However, phospholipid composition (as % of total) of the mitochondria was unaltered.
authors.affiliation: Department of Biochemistry, Faculty of Science, M.S. University of Baroda Baroda, India.
authors.forename: D V
authors.initials: DV
authors.lastname: Parmar
authors.forename: G
authors.initials: G
authors.lastname: Ahmed
authors.forename: M A
authors.initials: MA
authors.lastname: Khandkar
authors.forename: S S
authors.initials: SS
authors.lastname: Katyare
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D002855:Chromatography, Thin Layer; D007700:Kinetics; D050356:Lipid Metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
chemical_list: D010743:Phospholipids; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000251:Adenosine Triphosphatases