Adenosine and adenosine triphosphate modulate the substrate binding affinity of glucose transporter GLUT1 in vitro.
Biochim Biophys Acta
; 1511(1): 123-33, 2001 Mar 09.
Article
em En
| MEDLINE
| ID: mdl-11248211
ABSTRACT
Evidence indicates that a large portion of the facilitative glucose transporter isoform GLUT1 in certain animal cells is kept inactive and activated in response to acute metabolic stresses. A reversible interaction of a certain inhibitor molecule with GLUT1 protein has been implicated in this process. In an effort to identify this putative GLUT1 inhibitor molecule, we studied here the effects of adenosine and adenosine triphosphate (ATP) on the binding of D-glucose to GLUT1 by assessing their abilities to displace cytochalasin B (CB), using purified GLUT1 in vesicles. At pH 7.4, adenosine competitively inhibited CB binding to GLUT1 and also reduced the substrate binding affinity by more than an order of magnitude, both with an apparent dissociation constant (K(D)) of 3.0 mM. ATP had no effect on CB and D-glucose binding to GLUT1, but reduced adenosine binding affinity to GLUT1 by 2-fold with a K(D) of 30 mM. At pH 3.6, however, ATP inhibited the CB binding nearly competitively, and increased the substrate binding affinity by 4--5-fold, both with an apparent K(D) of 1.22 mM. These findings clearly demonstrate that adenosine and ATP interact with GLUT1 in vitro and modulate its substrate binding affinity. They also suggest that adenosine and ATP may regulate GLUT1 intrinsic activity in certain cells where adenosine reduces the substrate-binding affinity while ATP increases the substrate-binding affinity by interfering with the adenosine effect and/or by enhancing the substrate-binding affinity at an acidic compartment.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte de Monossacarídeos
/
Adenosina
/
Trifosfato de Adenosina
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos