Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II.
J Physiol
; 590(10): 2333-51, 2012 May 15.
Article
em En
| MEDLINE
| ID: mdl-22451434
ABSTRACT
Rapid exchange of metabolites between different cell types is crucial for energy homeostasis of the brain. Besides glucose, lactate is a major metabolite in the brain and is primarily produced in astrocytes. In the present study, we report that carbonic anhydrase 2 (CAII) enhances both influx and efflux of lactate in mouse cerebellar astrocytes. The augmentation of lactate transport is independent of the enzyme's catalytic activity, but requires direct binding of CAII to the C-terminal of the monocarboxylate transporter MCT1, one of the major lactate/proton cotransporters in astrocytes and most tissues. By employing its intramolecular proton shuttle, CAII, bound to MCT1, can act as a 'proton collecting antenna' for the transporter, suppressing the formation of proton microdomains at the transporter-pore and thereby enhancing lactate flux. By this mechanism CAII could enhance transfer of lactate between astrocytes and neurons and thus provide the neurons with an increased supply of energy substrate.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cerebelo
/
Astrócitos
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Ácido Láctico
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Anidrase Carbônica II
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Transportadores de Ácidos Monocarboxílicos
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Simportadores
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article