D-glucose and other monosaccharides are hydrophilic substances
that cannot easily cross the lipophilic bilayer of the cell membrane. Since
carbohydrates are most important for supplying energy to essentially
all cell types, specific transport mechanisms have evolved. While
vesicle-associated glucose transport has been described only recently,1-4 transporter proteins
have been known for years. Such proteins are embedded into the cell
membrane and function as hydrophilic pores that allow cellular uptake
and release and allow transcellular transport of monosaccharides.
Glucose transporter proteins can be divided into two groups:
(1) Sodium-dependent glucose transporters (SGLTs, symporter systems,
secondary “active” transporters), which are members
of the solute carrier family 5 (SLC5), couple sugar transport to
the electrochemical gradient of sodium and hence can transport glucose
against its own concentration gradient (eFig.
157.1); and (2) facilitative glucose transporters (GLUTs, uniporter
systems, “passive” transporters) are members of
the SLC2 family that can transport monosaccharides only along an
existing gradient (eFig. 157.2). To date,
five congenital defects of monosaccharide transport are known (Fig. 157-1). Their clinical picture is the
consequence of tissue-specific expression and substrate specificity
of the affected transporter.
Schematic presentation of transport mediated by a sodium-dependent glucose
transporter (SGLT) protein. Energy for this process is provided
by the action of the sodium/potassium ATPase located at
the basolateral side of the cell membrane exporting three sodium
ions for the influx of two potassium ions and thus generating an
electrical and a chemical gradient. Transport of glucose (or other
monosaccharides) at the apical membrane is coupled to the transport
of sodium (for details, see Fig. 157-4).
While sodium ions here are transported because of the low concentration
and the negative charge within the cell, glucose can be transported
against its own gradient. Transport for glucose is therefore termed secondary
Schematic presentation of transport mediated by a facilitative
glucose transporter (GLUT) protein. GLUT proteins are embedded into
the cell membrane, where they can be found in two conformations,
with an open side directed to either the outside or the inside of
the cell. Affinity of glucose (or other monosaccharides) to the
transporter on both sides can be characterized by specific equilibrium
constants. Net transport is possible only in the direction of the
lower concentration of the sugar.
Overview of glucose transporters within the human organism.
Transport across cell membranes is depicted by arrows, and specific
transporters are shown as symbols: rounded symbols are used for
sodium-dependent, secondary “active” transporters
(SGLTs); angular symbols are used for facilitative, “passive” transporters
(GLUTs). Red symbols represent the known defects of SGLT1 (glucose-galactose
malabsorption), SGLT2 (familial renal glucosuria), GLUT1 (glucose
transporter-1 deficiency), and GLUT2 (Fanconi-Bickel syndrome).