Altered kinetic properties of liver mitochondrial membrane-bound enzyme activities following paracetamol hepatotoxicity in the rat.

The effects of treatment with subtoxic (375 mg/kg) and toxic (750 mg/kg) doses of paracetamol on NADH oxidase, succinoxidase and Mg2+-ATPase activities in rat liver submitochondrial particles were examined. In the NADH oxidase system, treatment with subtoxic doses of paracetamol resulted in a 37% increase in activation energy in the high temperature range (E1) while the phase transition temperature (Tt) for this system decreased by 9°C. Subtoxic doses caused a 43% decrease in E1. For the succinoxidase system, Tt decreased by 2·4 to 3·4°C after paracetamol administration. E2 increased by 42% only in the subtoxic-treatment group while E1 remained unaltered in both paracetamol-treated groups. For the Mg2+-ATPase system, subtoxic doses of paracetamol treatment did not change the values of E1, E2 and Tt whereas toxic dose treatment resulted in a 29% decrease in E2 with a concomitant increase in Tt by 2·4°C without any change in the value of E1 · The results thus suggest that treatment with toxic and subtoxic doses of paracetamol results in possible differential alterations in the membrane lipid milieu.

Altered kinetic properties of rat heart mitochondrial enzymes following experimental-thyrotoxicosis.

Effects of T3- and T4-induced thyrotoxicosis on temperature-dependent Arrhenius kinetics of succinate oxidase and Mg2+- and Mg2+ + 2,4-dinitrophenoldependent ATPase activities in rat heart mitochondria were examined, For succinate oxidase system, treatment with T3 and T4 caused increase in the energy of activation in high temperature range in a dose-dependent manner. For low temperature range, increase in energy of activation was apparent only with higher doses of the hormones; with low doses a small but reproducible decrease was evinced. The phase transition temperature decreased significantly under these conditions. For the Mg2+- and Mg2++2,4-dintrophenol- dependent-ATPase activities, the activation energy values in high temperature range decreased in general. Activation energy values in low temperature range recorded a generalized increase in the Mg2+-ATPase enzyme system while the value did not change significantly for the Mg2+ + 2,4-dinitrophenol-ATPase; phase transition temperature registered a small but reproducible decrease under these conditions. The results are suggestive of increased membrane fluidization possibly through increased proportion of unsaturated fatty acids. The differential effects seen for succinate oxidase and ATPase systems are consistent with different lipid protein domains of these enzyme systems.