INCREASED BIOSYNTHESIS OF COA IN THE LIVER OF RATS TREATED WITH CLOFIBRATE

The amounts of CoA in rat liver increased about three fold after treatment with clofibrate. About 10 of total CoA were long‐chain acyl‐CoA in normal rats, and slightly less in clofibrate‐treated animals. The wet weight and protein content of the liver increased by about 25%. From livers of clofibrate‐treated rats, mitochondrial and lysosomal fractions were obtained in increased amounts by conventional tissue fractionation techniques. The supernatants from such livers had rather high activities of marker enzymes for lysosomes and peroxisomes. No changes of the specific activities of the two first enzymes in the degradation pathway for CoA, i.e. acid phosphatase and nucleotide pyrophosphatase, were found in the liver homogenate from clofibrate‐treated rats. In the mitochondrial fraction from such livers, both (contaminating) activities were decreased. The degradation of CoA was increased in the supernatant, however, probably because of an increased leakage of acid phosphatase from lysosomes during the fractionation procedure. The synthesis of CoA from pantothenic acid was estimated by two different methods in vitro: by quantitation of CoA formed and by estimation of the incorporation of [14C]pantothenic acid into CoA. By both methods, CoA synthesis was found to be increased 3–4‐fold in livers from clofibrate‐treated rats. Dephospho‐CoA kinase was found to have a dual localization, with a minor pool in the mitochondrial fraction. This enzyme was only slightly increased in the clofibrate‐treated animals. The activity of pantothenate kinase was more than doubled after clofibrate treatment. This is thought to be the most important factor for the increase of CoA. CoA exerted feed‐back inhibition at this step in liver supernatant from normal and clofibrate‐treated rats. Copyright © 1979, Wiley Blackwell. All rights reserved