Question

Explain how ketone bodies are degradeded in the matrix of brain mitochondria.

Answer 1

Under fasting conditions, the mean total circulating ketone body concentration is approximately in the range of 5.8 to 9.7 mmol/L in humans. Ketone bodies can replace glucose to a high degree. Thus, up to 60% of the human brain energy requirement can be matched by ketone body oxidation at prolonged fasting. Permeation of ketone bodies across the Blood-Brain-Barrier is mostly mediated by the monocarboxylate transporters i.e.,MCT1-2. Both, beta-hydroxybutyrate and acetoacetate are converted into acetyl-CoA in the cytosol as well as in the mitochondrial matrix.

Low-level oxidation of long-chain fatty acids are degraded by the brain mitochondria and there is a  observation that brain mitochondria do not use long-chain fatty acids of high level oxidation as hydrogen source. Therefore, low-level oxidation of long-chain fatty acids by isolated brain mitochondria has been attributed to: (i) The low translocation rate of long-chain fatty acid-CoA esters across inner mitochondrial membrane and (ii) The low enzymatic capacity of the β-oxidation pathway.