Journal
JOURNAL OF NEUROSCIENCE
Volume 30, Issue 42, Pages 13983-13991Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2040-10.2010
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Funding
- National Institutes of Health (NIH) [R01-NS037527, K02-AA13430, R01-AG23686, P01-DK68229]
- Howard Hughes Medical Institute
- Keck Foundation
- NIH/National Center for Research Resources/General Clinical Research Center [M01-RR00125]
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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.
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