Journal
NMR IN BIOMEDICINE
Volume 28, Issue 9, Pages 1111-1116Publisher
WILEY
DOI: 10.1002/nbm.3355
Keywords
ketogenic substrate; C-13-MRS; energy metabolism; lactate
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/SAU-MET/111398/2009, PTDC/SAU-NSC/122254/2010]
- Santa Casa da Misericordia, QREN [CENTRO-07-ST24-FEDER-002006]
- US Army Research Office
- Defense Advanced Research Projects Agency [W911NF-10-1-0059]
- structural funding for the Center for Neurosciences - European Regional Development Fund (FEDER) through program COMPETE [PEst-C/SAU/LA0001/2011]
- National Programme for Scientific Re-equipment [REDE/1517/RMN/2005]
- POCI (FEDER)
- FCT
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-MET/111398/2009, PTDC/SAU-NSC/122254/2010] Funding Source: FCT
Ask authors/readers for more resources
Ketone bodies can be used for cerebral energy generation in situ, when their availability is increased as during fasting or ingestion of a ketogenic diet. However, it is not known how effectively ketone bodies compete with glucose, lactate, and pyruvate for energy generation in the brain parenchyma. Hence, the contributions of exogenous 5.0mM [1-C-13]glucose and 1.0mM [2-C-13]lactate+0.1mM pyruvate (combined [2-C-13]lactate+[2-C-13]pyruvate) to acetyl-CoA production were measured both without and with 5.0mM [U-C-13]3-hydroxybutyrate in superfused rat hippocampal slices by C-13 NMR non-steady-state isotopomer analysis of tissue glutamate and GABA. Without [U-C-13]3-hydroxybutyrate, glucose, combined lactate+pyruvate, and unlabeled endogenous sources contributed (mean +/- SEM) 70 +/- 7%, 10 +/- 2%, and 20 +/- 8% of acetyl-CoA, respectively. With [U-C-13]3-hydroxybutyrate, glucose contributions significantly fell from 70 +/- 7% to 21 +/- 3% (p<0.0001), combined lactate+pyruvate and endogenous contributions were unchanged, and [U-C-13]3-hydroxybutyrate became the major acetyl-CoA contributor (68 +/- 3%) - about three-times higher than glucose. A direct analysis of the GABA carbon 2 multiplet revealed that [U-C-13]3-hydroxybutyrate contributed approximately the same acetyl-CoA fraction as glucose, indicating that it was less avidly oxidized by GABAergic than glutamatergic neurons. The appearance of superfusate lactate derived from glycolysis of [1-C-13]glucose did not decrease significantly in the presence of 3-hydroxybutyrate, hence total glycolytic flux (Krebs cycle inflow+exogenous lactate formation) was attenuated by 3-hydroxybutyrate. This indicates that, under these conditions, 3-hydroxybutyrate inhibited glycolytic flux upstream of pyruvate kinase. Copyright (c) 2015 John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available