The Contribution of Blood Lactate to Brain Energy Metabolism in Humans Measured by Dynamic 13C Nuclear Magnetic Resonance Spectroscopy

被引:257
作者
Boumezbeur, Fawzi [1 ,2 ]
Petersen, Kitt F. [3 ]
Cline, Gary W. [3 ]
Mason, Graeme F. [2 ,4 ]
Behar, Kevin L. [2 ,4 ]
Shulman, Gerald I. [3 ,6 ]
Rothman, Douglas L. [2 ,5 ]
机构
[1] CEA, NeuroSpin, Ctr Saclay, Inst Imagerie Biomed,I2BM, F-91191 Gif Sur Yvette, France
[2] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA
[4] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA
[5] Yale Univ, Sch Med, Dept Biomed Engn, New Haven, CT 06520 USA
[6] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, Howard Hughes Med Inst, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
TRICARBOXYLIC-ACID CYCLE; KETOGLUTARATE GLUTAMATE EXCHANGE; HUMAN VISUAL-CORTEX; IN-VIVO; RAT-BRAIN; GLUCOSE-TRANSPORT; BETA-HYDROXYBUTYRATE; IMAGE SEGMENTATION; NMR-SPECTROSCOPY; WHITE-MATTER;
D O I
10.1523/JNEUROSCI.2040-10.2010
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To determine whether plasma lactate can be a significant fuel for human brain energy metabolism, infusions of [3-C-13] lactate and H-1-C-13 polarization transfer spectroscopy were used to detect the entry and utilization of lactate. During the 2 h infusion study, C-13 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 unidirectionaltransport(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 similar to 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 mu mol.g(-1).min(-1) (68% confidence interval); and (4) the majority of plasma lactate is metabolized in neurons similar to glucose.
引用
收藏
页码:13983 / 13991
页数:9
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