The oxidation of glucose, ketone bodies and acetate by the brain of normal and ketonaemic sheep.

1. The utilization and oxidation of glucose, acetate and ketone bodies by the brain of sheep has been determined from measurements of arteriovenous (A-V) differences and cerebral blood flow, as well as by infusing 14C-labelled metabolites. 2. The A-V difference for glucose was generally more than one sixth, on a molar basis, that of oxygen. 3. The mean rate of glucose utilization by the brain of conscious sheep (0-508 +/- 0-063 mumole/g per minute) was maintained even when the capillary glucose concentration was below 1-4 mM. 4. The amount of 14CO2 produced from [U-14C]glucose by the brain was consistent with glucose being the only energy source for the brain, even during hypoglycaemia and hyperketonaemia. 5. There was no appreciable production of lactate or pyruvate by the brain. 6. There was no significant A-V difference for acetate across the brain in normal or undernourished pregnant sheep. The small A-V differences that were measured show that less than 5% of the CO2 produced could be derived from acetate, a conclusion that is supported by experiments using [U-14C]acetate. 7. No significant A-V difference was detectable across the brain for 3-hydroxybutyrate or acetoacetate in normal fed, pregnant ketonaemic or even anaesthetized sheep infused with acetoacetate. Experiments in which [U-14C]-D(-)-3-hydroxybutyrate was infused also showed that less than 5% of CO2 was derived from ketone bodies. 8. In anaesthetized sheep infused with acetoacetate, measurements were made simultaneously across brain, heart and skeletal muscle. In contrast to the non-significant uptake of ketone bodies by the brain, uptake by heart and skeletal muscle was sufficient to account for nearly 60% of their oxygen consumption. 9. Experiments using [14C]hydroxybutyrate confirmed that during infusion of acetoacetate most of the CO2 produced by the heart, but not by the brain, was derived from ketone bodies. 10. In anaesthetized sheep ketone bodies penetrate only slowly into cerebrospinal fluid. 11. It is proposed that mechanisms for the utilization of ketones by the sheep brain have not evolved because glucose utilization by the brain is a smaller fraction of whole body glucose utilization than in man and rats.