Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model.

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Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_3D84CC3809FF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model.
Périodique
Frontiers in Neuroenergetics
Auteur⸱e⸱s
Duarte J.M., Morgenthaler F.D., Lei H., Poitry-Yamate C., Gruetter R.
ISSN
1662-6427 (Electronic)
ISSN-L
1662-6427
Statut éditorial
Publié
Date de publication
2009
Volume
1
Pages
6
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Glucose supply from blood to brain occurs through facilitative transporter proteins. A near linear relation between brain and plasma glucose has been experimentally determined and described by a reversible model of enzyme kinetics. A conformational four-state exchange model accounting for trans-acceleration and asymmetry of the carrier was included in a recently developed multi-compartmental model of glucose transport. Based on this model, we demonstrate that brain glucose (G(brain)) as function of plasma glucose (G(plasma)) can be described by a single analytical equation namely comprising three kinetic compartments: blood, endothelial cells and brain. Transport was described by four parameters: apparent half saturation constant K(t), apparent maximum rate constant T(max), glucose consumption rate CMR(glc), and the iso-inhibition constant K(ii) that suggests G(brain) as inhibitor of the isomerisation of the unloaded carrier. Previous published data, where G(brain) was quantified as a function of plasma glucose by either biochemical methods or NMR spectroscopy, were used to determine the aforementioned kinetic parameters. Glucose transport was characterized by K(t) ranging from 1.5 to 3.5 mM, T(max)/CMR(glc) from 4.6 to 5.6, and K(ii) from 51 to 149 mM. It was noteworthy that K(t) was on the order of a few mM, as previously determined from the reversible model. The conformational four-state exchange model of glucose transport into the brain includes both efflux and transport inhibition by G(brain), predicting that G(brain) eventually approaches a maximum concentration. However, since K(ii) largely exceeds G(plasma), iso-inhibition is unlikely to be of substantial importance for plasma glucose below 25 mM. As a consequence, the reversible model can account for most experimental observations under euglycaemia and moderate cases of hypo- and hyperglycaemia.
Pubmed
Open Access
Oui
Création de la notice
04/08/2010 15:28
Dernière modification de la notice
20/08/2019 13:33
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