Mitochondrial ATPase: a target for paracetamol-induced hepatotoxicity

Abstract

We examined the effect of paracetamol treatment (650 mg/kg) on the function of the 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 K_m for the intermediate and low affinity components decreased by about 30% without change in V_max, which may represent a compensatory mechanism. The drug treatment also resulted in a dramatic decrease in the phase transition temperature by about 19°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 phopholipid/cholesterol molar ratio increased by 50% after paracetamol treatment. However, phospholipid composition (as % of total) of the mitochondria was unaltered.