Figure 1

(A) Simplified diagram of cerebral ketone body metabolism. At times of glucose shortage, such as prolonged fasting, ketone bodies are an important energy source for the brain. The oxidoreductase 3-hydroxybutyrate dehydrogenase (BDH) mediates the first step of ketone body degradation, between 3-hydroxybutyrate and acetoacetate. 3-oxoacid-CoA transferase 1 (OXCT1) catalyzes the transfer of coenzyme A from succinyl-CoA to acetoacetate, generating acetoacetyl-CoA. Via acetyl-CoA acetyltransferase 1 (ACAT1), acetoacetyl-CoA is converted into two molecules of acetyl-CoA, which then enter the citric acid cycle. The utilization of ketone bodies results in an elevation of intracellular succinate, leading to HIF-1α stabilization via product inhibition of prolyl hydroxylases (PHD). Furthermore, ketone bodies provide substrates for the synthesis of various molecules, especially lipids. In this regard, acetoacetyl-CoA is formed in the cytoplasm from acetoacetate by the action of acetoacetyl-CoA synthetase (AACS). (B) The expression of the ketone body metabolizing enzymes was analyzed in five glioma cell lines as well as in normal brain (gray, gray matter; white, white matter) by real-time quantitative PCR. Results are presented as the fold change in gene expression normalized to the internal control 18S rRNA (mean and standard deviation; n.d., not detectable).