[2,4-13C2]-β-hydroxybutyrate metabolism in human brain

Infusions of [2,4-C-13(2)]-beta-hydroxybutyrate and H-1-C-13 polarization transfer spectroscopy were used in normal human subjects to detect the entry and metabolism of beta-hydroxybutyrate in the brain. During the 2-hour infusion study, C-13 label was detectable in the beta-hydroxybutyrate resonance positions and in the amino acid pools of glutamate, glutamine, and aspartate. With a plasma concentration of 2.25 +/- 0.24 mmol/L (four volunteers), the apparent tissue beta-hydroxybutyrate concentration reached 0.18 +/- 0.06 mmol/L during the last 20 minutes of the study. The relative fractional enrichment of C-13-4-glutamate labeling was 6.78 +/- 1.71 %, whereas C-13-4-glutamine was 5.68 +/- 1.84%. Steady-state modeling of the C-13 label distribution in glutamate and glutamine suggests that, under these conditions, the consumption of the beta-hydroxybutyrate is predominantly neuronal, used at a rate of 0.032 +/- 0.009 mmol (.) k(-1) (.) min(-1), and accounts for 6.4 +/- 1.6% of total acetyl coenzyme A oxidation. These results are consistent with minimal accumulation of cerebral ketones with rapid utilization, implying blood-brain barrier control of ketone oxidation in the nonfasted adult human brain.