The human erythrocyte sugar transporter presents two sugar import sites

The human erythrocyte sugar transporter presents sugar import (e2) and suga r export (e1) sites simultaneously. This study asks whether the sugar trans porter exposes only one or multiple import sites. We approached this questi on by analysis of cytochalasin B binding to the human erythrocyte sugar exp ort site in the presence of sugars that bind to the sugar import site. Extr acellular maltose does not enter human erythrocytes. High concentrations of maltose (1-100 mM) inhibit cytochalasin B binding to human red cells. Low concentrations (25 -500 mu M) increase the level of erythrocyte cytochalasi n B binding. Maltose modulation of cytochalasin B binding is mediated by al tered affinity of sugar export sites for cytochalasin B. Similar results ar e obtained with other cell-impermeant inhibitors of sugar uptake. Extracell ular D-glucose (a transported sugar) stimulates cytochalasin B binding at l ow D-glucose concentrations (10-250 mu M), but this effect is lost at highe r concentrations. Intracellular D-glucose inhibits cytochalasin B binding. Low concentrations of extracellular maltose and other nontransported inhibi tors stimulate 3-O-methylglucose uptake in erythrocytes. Higher sugar conce ntrations (1-100 mM) inhibit transport. These data support the hypothesis t hat the erythrocyte sugar transporter presents two sugar import sites and a t least one sugar export site. This conclusion is consistent with the propo sed oligomeric structure of the sugar transporter, a complex of four GluT1 proteins in which each subunit presents a translocation pathway.