[2,4-13C2]-β-Hydroxybutyrate Metabolism in Human Brain

• Published in: Journal of cerebral blood flow and metabolism 2002-07, Vol.22 (7), p.890-898
• Main Authors: Pan, Jullie W., de Graaf, Robin A., Petersen, Kitt F., Shulman, Gerald I., Hetherington, Hoby P., Rothman, Douglas L.
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - administration & dosage; 3-Hydroxybutyric Acid - metabolism; Acetyl Coenzyme A - metabolism; Aspartic Acid - metabolism; Biochemistry and metabolism; Biological and medical sciences; Blood-Brain Barrier; Brain - metabolism; Carbon Isotopes; Central nervous system; Fundamental and applied biological sciences. Psychology; Glutamic Acid - metabolism; Glutamine - metabolism; Humans; Ketones - metabolism; Kinetics; Magnetic Resonance Spectroscopy; Neurons - metabolism; Oxidation-Reduction; Vertebrates: nervous system and sense organs
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-200207000-00014

Infusions of [2,4-13C2]-β-hydroxybutyrate and 1H–13C polarization transfer spectroscopy were used in normal human subjects to detect the entry and metabolism of β-hydroxybutyrate in the brain. During the 2-hour infusion study, 13C label was detectable in the β-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 β-hydroxybutyrate concentration reached 0.18 ± 0.06 mmol/L during the last 20 minutes of the study. The relative fractional enrichment of 13C-4-glutamate labeling was 6.78 ± 1.71%, whereas 13C-4-glutamine was 5.68 ± 1.84%. Steady-state modeling of the 13C label distribution in glutamate and glutamine suggests that, under these conditions, the consumption of the β-hydroxybutyrate is predominantly neuronal, used at a rate of 0.032 ± 0.009 mmol · kg−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.