GLUTs are integral membrane proteins that contain 12 membrane-spanning
helices with both the amino and
carboxyl termini exposed on the
cytoplasmic side of the
plasma membrane. GLUT proteins transport
glucose and related
hexoses according to a model of alternate conformation, which predicts that the transporter exposes a single
substrate binding site toward either the outside or the inside of the cell. Binding of glucose to one site provokes a
conformational change associated with transport, and releases glucose to the other side of the membrane. The inner and outer glucose-binding sites are, it seems, located in transmembrane segments 9, 10, 11; also, the
DLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.
Types Each glucose transporter
isoform plays a specific role in glucose metabolism determined by its pattern of tissue expression, substrate specificity, transport kinetics, and regulated expression in different physiological conditions. To date, 14 members of the GLUT/SLC2 have been identified. On the basis of sequence similarities, the GLUT family has been divided into three subclasses.
Class I Class I comprises the well-characterized glucose transporters GLUT1-GLUT4.
Classes II/III Class II comprises: •
GLUT5 (), a
fructose transporter in
enterocytes •
GLUT7 (), found in the small and large intestine, •
GLUT9 (), recently has been found to transport
uric acid •
GLUT11 () Class III comprises: •
GLUT6 (), •
GLUT8 (), •
GLUT10 (), •
GLUT12 (), and •
GLUT13, also H+/
myo-inositol transporter HMIT (), primarily expressed in brain.
Crane's discovery of
cotransport was the first ever proposal of flux coupling in biology.
Crane in 1961 was the first to formulate the cotransport concept to explain active transport. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the
brush border membrane was [is] coupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined, and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type. ==See also==