[2,4-13 C2 ]-beta-Hydroxybutyrate metabolism in human brain.
Infusions of [2,4-13C2]-beta-hydroxybutyrate and 1H-13C 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, 13C 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 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 beta-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.
Pan
Jullie W
JW
Albert Einstein College of Medicine, Bronx, New York 10461, USA. jpan@aecom.yu.edu
de Graaf
Robin A
RA
Petersen
Kitt F
KF
Shulman
Gerald I
GI
Hetherington
Hoby P
HP
Rothman
Douglas L
DL
D020155:3-Hydroxybutyric Acid / Q000008:administration & dosage / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007659:Ketones / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009474:Neurons / Q000378:metabolism; D010084:Oxidation-Reduction
D002247:Carbon Isotopes; D007659:Ketones; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D000105:Acetyl Coenzyme A; D020155:3-Hydroxybutyric Acid