Location: Mackenzie, Loo, Panayotova-Heiermann and Wright, 1996 @ b0a32e5099ae / documentation.html
- Author:
- David Nickerson <nickerso@users.sourceforge.net>
- Date:
- 2015-02-27 21:27:56+13:00
- Desc:
- adding a preliminary documentation page which includes the previous tmp-doc generated documentation and some annotations
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/mackenzie_loo_panayotova-heiermann_wright_1996/rawfile/b0a32e5099ae46cec773763490f3c6a48d4a2d4c/documentation.html
Annotations
- Described by
- Biophysical Characteristics of the Pig Kidney Na/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2, M. Mackenzie, D.D.F. Loo, M. Panayotova-Heiermann, and E. M. Wright, 1996, Journal of Biological Chemistry, 271, 32678-32683. DOI: 10.1074/jbc.271.51.32678
- Protein
- Sodium/glucose cotransporter 2 (mouse)
- Sodium/glucose cotransporter 2 (human)
- Low affinity Na-dependent glucose transporter SGLT2 delta e trans (rat)
- Located in
- Proximal convoluted tubule
- Apical plasma membrane
- Epithelial cell of proximal tubule
- Proximal straight tubule
Model Status
This CellML model has been curated, the units are consistent and the model runs in COR and PCEnv. This model recreates the published results.
Model Structure
Abstract: The Na-dependent, low affinity glucose transporter SGLT2 cloned from pig kidney is 76% identical (at the amino acid level) to its high affinity homologue SGLT1. Using two-microelectrode voltage clamp, we have characterized the presteady-state and steady-state kinetics of SGLT2 expressed in Xenopus oocytes. The kinetic properties of the steady-state sugar-evoked currents as a function of external Na and a-methyl-D-glucopyranoside (aMG) concentrations were consistent with an ordered, simultaneous transport model in which Na binds first. Na binding was voltage-dependent and saturated with hyperpolarizing voltages. Phlorizin was a potent inhibitor of the sugar-evoked currents (Ki ~10 mM) and blocked an inward Na current in the absence of sugar. SGLT2 exhibited Na-dependent presteadystate currents with time constants 3-7 ms. Charge movements were described by Boltzmann relations with apparent valence ~1 and maximal charge transfer ~11 nC, and were reduced by the addition of sugar or phlorizin. The differences between SGLT1 and SGLT2 were that (i) the apparent affinity constant (K0.5) for aMG (~3 mM) was an order of magnitude higher for SGLT2; (ii) SGLT2 excluded galactose, suggesting discrete sugar binding; (iii) K0.5 for Na was lower in SGLT2; and (iv) the Hill coefficient for Na was 1 for SGLT2 but 2 for SGLT1. Simulations of the six-state kinetic model previously proposed for SGLT1 indicated that many of the kinetic properties observed in SGLT2 are expected by simply reducing the Na/glucose coupling from 2 to 1.
The original paper reference is cited below:
Biophysical Characteristics of the Pig Kidney Na/Glucose Cotransporter SGLT2 Reveal a Common Mechanism for SGLT1 and SGLT2, M. Mackenzie, D.D.F. Loo, M. Panayotova-Heiermann, and E. M. Wright, 1996, Journal of Biological Chemistry, 271, 32678-32683. DOI: 10.1074/jbc.271.51.32678
