The in Viuo Utilization of Acetoacetate, m( -)-3-Hydroxybutyrate, and Glucose for Lipid Synthesis in Brain in the l&Day-old Rat

Previously, we have shown the preferential incorporation of label from [3-‘%]acetoacetate, D-( -)-3-hydroxy[3-%]butyrate, and [2-‘4C]glucose into sterols and fatty acids in brain in Id-day-old rats. In these experiments, we assumed that the labeled metabolites would be used from the blood in the form which was injected. However, during metabolic processes, a labeled metabolite which is present in the blood may be converted into another metabolite which is more readily utilized. We investigated the possibility of this interconversion or “cross-labeling” of acetoacetate, D(-)-3-hydroxybutyrate, and glucose as a function of time after the injection of [3-‘4C]acetoacetate, D-(-)-3hydroxy[3-‘4C]butyrate, [2-‘4C]glucose, and [l-‘4C]octanoate. The amount of 14C incorporated from each of these labeled precursors and from [2-14C]acetate into sterols and fatty acids in brain as a function of time was measured in the 18-day-old rat. The amount of 3H incorporated into sterols and fatty acids in brain as a function of age was measured after the injection of 3Hz0 proportional to body weight in rats 6 to 30 days of age to determine the age at which lipid synthesis is greatest in whole brain. 1) Neither acetoacetate nor D(-)-3-hydroxybutyrate in blood in Is-day-old rats contained label by 150 min after the injection of [2-14C]glucose. However, after the injection of either [3-14C]acetoacetate or D-(-)-3-hydroxy[3-‘4C]buQrate, glucose in blood contained label. 2) D-( -)-3-Hydroxybutyrate in blood contained label almost immediately after the injection of [3-‘4C]acetoacetate. The ratios of the specific activity of acetoacetate to the specific activity of D-(-)-3-hydroxybutyrate as a function of time were not constant. This indicates that acetoacetate and D(-)-3-hydroxybutyrate are not in rapid equilibrium. 3) Acetoacetate in blood contained label after the injection of D-(-)-3-hydroxy[3-‘4C]butyrate. The ratios of the specific activity of acetoacetate to the specific activity of D-( -)-3-hydroxybutyrate were not constant as a function of time and were distinct from the ratios observed after the injection of [3-‘4C]acetoacetate. 4) However, glucose, acetoacetate, and D-(-)-3-hydroxybutyrate in blood contained label after the injection of