Chapter 6 Mechanisms of active and passive transport in a family of homologous sugar transporters found in both prokaryotes and eukaryotes

Abstract

This chapter focuses on the human erythrocyte glucose transporter (GLUT- l). The protein GLUT-1 belongs to a family of five homologous, passive glucose transporters identified by cDNA cloning in mammalian tissues. Each of these isoforms has a different tissue distribution, reflecting its unique physiological role. The comparison of the amino acid sequences of these homologous proteins has identified residues that might be involved in the translocation mechanism and should eventually lead to a better understanding of their differing physiological roles and regulation by hormones. The roles played by the various parts of the D-glucose molecule in its binding and translocation by the transporter have been studied using epimers, deoxy-sugars, and fluoro-substituted sugars in which the fluorine atom can serve as a hydrogen-bond acceptor. The affinity of these analogues for the transporter has been investigated in a number of ways, including the measurement of their transport, their inhibition of the transport of other sugars and their inhibition of stereospecific D-glucose binding to erythrocyte membranes.