Energy-based bond graph models of glucose transport with SLC transporters

Abstract

The SLC (solute carrier) superfamily mediates the passive transport of small molecules across apical and basolateral cell membranes in nearly all tissues. In this paper, we employ bond-graph approaches to develop models of SLC transporters that conserve mass, charge, and energy, respectively, and can be parameterized for a specific cell and tissue type for which the experimental kinetic data are available. We show how analytic expressions that preserve thermodynamic consistency can be derived for a representative four- or six-state model, given reasonable assumptions associated with steady-state flux conditions. We present details on fitting parameters for SLC2A2 (a GLUT transporter) and SLC5A1 (an SGLT transporter) to experimental data and show how well the steady-state flux expressions match the full kinetic analysis. Since the bond-graph approach will not be familiar to many readers, we provide a detailed description of the approach and illustrate its application to a number of familiar biophysical processes.