Hepatic ketone-body metabolism in developing sheep and pregnant ewes.

Abstract

1. In order to establish whether or not there is a relationship between the blood ketone-body concentrations and the potential ability of the liver to synthesize ketone bodies in sheep on varying nutritional regimens, a study has been made of the concentrations of acetoacetate and 3-hydroxybutyrate in blood and the activities of enzymes concerned with ketogenesis in liver of developing sheep from mid-way through gestation to maturity, in pregnant ewes from mid-way through pregnancy and in starved pregnant and non-pregnant ewes.2. During development the most marked change in blood 3-hydroxybutyrate concentration occurred when the lambs were weaned. Blood acetoacetate concentrations did not change during development. When mature ewes were starved both 3-hydroxybutyrate and acetoacetate concentrations in blood were increased.3. Changes found in the activity of 3-hydroxybutyrate dehydrogenase (EC1.1.1.30) in the liver were correlated with the changes in blood 3-hydroxybutyrate concentrations during development but no such relationship existed in pregnant or fasted ewes. No correlation was found between the ability of the liver to synthesize acetoacetate and blood ketone body concentrations in either developing or pregnant adult sheep. The rate of acetoacetate production expressed per g liver increased during foetal life but values observed in lambs 1 d after birth were similar to those found in suckling and mature sheep. During the last month of pregnancy and when non-pregnant sheep were starved the hepatic potential for ketogenesis was increased. During development the activity of acetyl-CoA acetyltransferase (EC2.3.1.9) was correlated with the rate of hepatic acetoacetate production.4. These changes have been contrasted with those that occur in developing and starved adult rats.5. It is concluded that hepatic production of ketone bodies cannot be the only factor in the regulation of blood ketone body concentrations in developing and pregnant sheep.