A subcellular study of the clofibratei-nduced increase in coenzyme a concentration in rat liver

Abstract

When clofibrate [ethyl 2-(4-chlorophenoxv)-2-methylpropionatel was administered subcutaneously to rats (600 mg kg per day for 3 days), the concentration of CoA and its acyl derivatives in the liver increased 2.5-fold. Forty-eight per cent of the total cellular CoA in the clofibrate-treated rat liver and 51 per cent in the control liver was found in the mitochondrial fraction. In order to study the intermediates of CoA synthesis, clofibrate-treated rats were injected with [ 3H]pantothenate intracardially and killed after 30 min, l or 2hr for determination of the incorporation of radioactivity into CoA and its precursors. The incorporation of pantothenate into CoA after 2 hr was 5.9-fold in the liver and 4.5-fold in the liver mitochondrial fraction as compared with the control values. Measurement of the pantothenate concentration and radioactivity in clofibrate-treated and control rat liver showed that the higher incorporation of [ 3H]pantothenate into CoA in clofibrate-treated rat liver cannot be the result of a higher specific radioactivity of pantothenate. It is therefore evident that clofibrate affects the CoA concentration by increasing the rate of synthesis, although the rate of CoA degradation is simultaneously decreased, as has been shown previously [9]. The present results indicate that clofibrate increases the total hepatic CoA concentration without affecting the intracellular compartmentation of CoA. The clofibrate-induced increase in the rate of CoA synthesis does not result in differences in the compartmentation of the intermediates of CoA synthesis.