Activities of enzymes of ketone-body utilization in brain and other tissues of suckling rats

Abstract

1. The activities of 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase in rat brain at birth were found to be about two-thirds of those of adult rat brain, expressed per g wet wt. The activities rose throughout the suckling period and at the time of weaning reached values about three times higher than those for adult brain. Later they gradually declined. 2. At birth the activity of acetoacetyl-CoA thiolase in rat brain was about 60% higher than in the adult. During the suckling period there was no significant change in activity. 3. In rat kidney the activities of the three enzymes at birth were less than one-third of those at maturity. They gradually rose and after 5 weeks approached the adult value. Similar results were obtained with rat heart. 4. The activity of glutamate dehydrogenase (a mitochondrial enzyme like 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase) also rose in brain and kidney during the suckling period, but at no stage did it exceed the adult value. 5. Throughout the suckling period the total ketone-body concentration in the blood was about six times higher than in adult fed rats, and the concentration of free fatty acids in the blood was three to four times higher. 6. It is concluded that the rate of ketone-body utilization in brains of suckling rats is determined by both the greater amounts of the key enzymes in the tissue and the high concentrations of ketone bodies in the blood. In addition, the low activities of the relevant enzymes in kidney and heart of suckling rats may make available more ketone bodies for the brain.

The Contribution of Ketone Bodies to Basal and Activity-Dependent Neuronal Oxidation in Vivo

“…Because total glucose utilization was not measured in the present study, we cannot say whether the reduction in V pdhN with increasing V AcCoA-kbN corresponded to reduced or unchanged glucose utilization (e.g., net lactate formation followed by efflux). Reduced brain glucose utilization and increased lactate efflux is seen during prolonged fasting-induced hyperketonemia in humans 32 and rats, 27 suggesting that a larger glycolytic component than we estimate based on pyruvate oxidation during maximum ketone use, cannot be fully excluded.…”

Cloning of rat brain succinyl-CoA:3-oxoacid CoA-transferase cDNA. Regulation of the mRNA in different rat tissues and during brain development

“…This is consistent with the unique developmental pattern of the ketone-body-metabolizing enzymes. The activity of these enzymes is relatively high at birth, increases about 3-5-fold and then declines at weaning to the adult level [4,5]. This is in contrast with the development of other mitochondrial enzymes, whose activities increase gradually from a low level at birth to the adult level during the first 3 weeks.…”

“…The recombinant plaques were screened with a 1: 1500 dilution of a specific polyclonal antibody to rat brain 3-oxoacid CoAtransferase [4] from which antigenic determinants to E. coli and coliphage A proteins were removed on an affinity column of E. coli lysate from BNN 97 linked to CNBrtreated Sepharose 4B [9]. Positive plaques containing 3-oxoacid CoA-transferase determinants were identified with peroxidase-conjugated goat anti-(rabbit IgG) [10].…”

Distinct physiological roles of animal succinate thiokinases Association of guanine nucleotide‐linked succinate thiokinase with ketone body utilization

“…The ability of the brain to use ketone bodies is not believed to be an enzymic adaptation, as the 216 [9]. Changes in the activity of STK in diabetes have not previously been studied, though it has been suggested that the availability of succinyl-CoA could control ketone body utilization [ 10,111.…”