Acetoacetate Metabolism in Rat Brain

1. Data are provided that indicate that the rat brain acetoacetyl-CoA deacylase is almost exclusively mitochondrial. Developmental studies show that this enzyme more than doubles its activity during suckling (0-21 days) and then maintains this activity in adults (approx. 1.1 units/g wet wt.). 2. Kinetic studies (on the acetoacetyl-CoA deacylase) in a purified brain mitochondrial preparation give a Vmax. of 47nmol/min per mg of protein, and a Km for acetoacetyl-CoA of 5.2pM and are compatible with substrate inhibition by acetoacetyl-CoA above concentrations of 47pM. 3. The total brain 3-hydroxy-3-methylglutaryl-CoA synthase remains constant in the developing and adult rat brain (approx. 1.2 units/g wet wt.). This enzyme is located in both the mitochondrial and cytosolic fractions. During suckling (0-21 days) the mitochondrial 3-hydroxy-3-methylglutarylCoA synthase represents approx. one-third of the total, but this increases markedly to about 60% ofthe total in the adult. The cytosolic enzyme correspondingly falls to approx. 40% of the total. 4. The role of the acetoacetyl-CoA deacylase in providing cytosolic acetoacetate for biosynthetic activities in the developing brain is discussed.