Deitmer, JW;
Theparambil, SM;
Ruminot, I;
Noor, SI;
Becker, HM;
(2019)
Energy Dynamics in the Brain: Contributions of Astrocytes to Metabolism and pH Homeostasis.
Frontiers in Neuroscience
, 13
, Article 1301. 10.3389/fnins.2019.01301.
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Abstract
Regulation of metabolism is complex and involves enzymes and membrane transporters, which form networks to support energy dynamics. Lactate, as a metabolic intermediate from glucose or glycogen breakdown, appears to play a major role as additional energetic substrate, which is shuttled between glycolytic and oxidative cells, both under hypoxic and normoxic conditions. Transport of lactate across the cell membrane is mediated by monocarboxylate transporters (MCTs) in cotransport with H+, which is a substrate, a signal and a modulator of metabolic processes. MCTs form a "transport metabolon" with carbonic anhydrases (CAs), which not only provide a rapid equilibrium between CO2, HCO3- and H+, but, in addition, enhances lactate transport, as found in Xenopus oocytes, employed as heterologous expression system, as well as in astrocytes and cancer cells. Functional interactions between different CA isoforms and MCTs have been found to be isoform-specific, independent of the enzyme's catalytic activity, and they require physical interaction between the proteins. CAs mediate between different states of metabolic acidosis, induced by glycolysis and oxidative phosphorylation, and play a relay function in coupling pH regulation and metabolism. In the brain, metabolic processes in astrocytes appear to be linked to bicarbonate transport and to neuronal activity. Here, we focus on physiological processes of energy dynamics in astrocytes as well as on the transfer of energetic substrates to neurons.
| Type: | Article |
|---|---|
| Title: | Energy Dynamics in the Brain: Contributions of Astrocytes to Metabolism and pH Homeostasis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnins.2019.01301 |
| Publisher version: | http://dx.doi.org/10.3389/fnins.2019.01301 |
| Language: | English |
| Additional information: | © 2019 Deitmer, Theparambil, Ruminot, Noor and Becker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | bicarbonate, carbonic anhydrases, glycolysis, lactate, monocarboxylate transporters, protons |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10114493 |
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