Formation of Ketone Bodies in the Perfused Rat Liver

Abstract

I would like to begin by explaining why I turned to the perfused whole organ after having used tissue slices, tissue homogenates, mitochondria and isolated enzyme systems for over 30 years. These various tissue preparations have proved satisfactory for the study of many aspects of metabolism, but they are of limited use in the study of the regulation of metabolic processes, especially the integrated control mechanisms of the functionally active organ. As is now known, key factors in these control mechanisms are the concentrations of intermediary metabolites and these depend on the intactness of the tissue structure. Metabolites are diluted on homogenisation, and are washed out of slices and isolated mitochondria. This can cause major losses of metabolic activities and what remains may represent only a small fraction of the original capacity.

The work reported in this contribution was carried out in collaboration with Dr. Patricia C. Wallace, Mr. R. Hems, Dr. W. Feldheim, Dr. R. A. Freedland, Dr. Lillian A. Jedeikin and Miss Deidre M. Keane.