The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy.
To determine whether plasma lactate can be a significant fuel for human brain energy metabolism, infusions of [3-(13)C]lactate and (1)H-(13)C polarization transfer spectroscopy were used to detect the entry and utilization of lactate. During the 2 h infusion study, (13)C incorporation in the amino acid pools of glutamate and glutamine were measured with a 5 min time resolution. With a plasma concentration ([Lac](P)) being in the 0.8-2.8 mmol/L range, the tissue lactate concentration ([Lac](B)) was assessed as well as the fractional contribution of lactate to brain energy metabolism (CMRlac). From the measured relationship between unidirectional lactate influx (V(in)) and plasma and brain lactate concentrations, lactate transport constants were calculated using a reversible Michaelis-Menten model. The results show that (1) in the physiological range, plasma lactate unidirectional transport (V(in)) and concentration in tissue increase close to linearly with the lactate concentration in plasma; (2) the maximum potential contribution of plasma lactate to brain metabolism is 10% under basal plasma lactate conditions of ∼1.0 mmol/L and as much as 60% at supraphysiological plasma lactate concentrations when the transporters are saturated; (3) the half-saturation constant K(T) is 5.1 ± 2.7 mmol/L and V(MAX) is 0.40 ± 0.13 μmol · g(-1) · min(-1) (68% confidence interval); and (4) the majority of plasma lactate is metabolized in neurons similar to glucose.
Departments of Diagnostic Radiology, Yale School of Medicine, New Haven, Connecticut 06520, USA. fawzi.boumezbeur@cea.fr
Fawzi
F
Boumezbeur
Kitt F
KF
Petersen
Gary W
GW
Cline
Graeme F
GF
Mason
Kevin L
KL
Behar
Gerald I
GI
Shulman
Douglas L
DL
Rothman
D000328:Adult; D000465:Algorithms; D001253:Astrocytes / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D002250:Carbon Radioisotopes; D003627:Data Interpretation, Statistical; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009778:Occipital Lobe / Q000166:cytology / Q000378:metabolism; D010296:Parietal Lobe / Q000378:metabolism; D014233:Tricarboxylic Acids / Q000378:metabolism; D055815:Young Adult
D002250:Carbon Radioisotopes; D014233:Tricarboxylic Acids; D019344:Lactic Acid; D005947:Glucose