2 3 4 5 6 7 8 9 10 11 12 13 14 External concentration of glucose (mM)

M EXPERIMENTAL FIGURE 7-3 Cellular uptake of glucose mediated by GLUT proteins exhibits simple enzyme kinetics and greatly exceeds the calculated rate of glucose entry solely by passive diffusion. The initial rate of glucose uptake (measured as micromoles per milliliter of cells per hour) in the first few seconds is plotted against increasing glucose concentration in the extracellular medium. In this experiment, the initial concentration of glucose in the cells is always zero. Both GLUT1, expressed by erythrocytes, and GLUT2, expressed by liver cells, greatly increase the rate of glucose uptake (red and orange curves) compared with that associated with passive diffusion (blue curve) at all external concentrations. Like enzyme-catalyzed reactions, GLUT-facilitated uptake of glucose exhibits a maximum rate (Vmax). The Km is the concentration at which the rate of glucose uptake is half maximal. GLUT2, with a Km of about 20 mM, has a much lower affinity for glucose than GLUT1, with a Km of about 1.5 mM

GLUT1 Uniporter Transports Glucose into Most Mammalian Cells

Most mammalian cells use blood glucose as the major source of cellular energy and express GLUT1. Since the glucose concentration usually is higher in the extracellular medium (blood in the case of erythrocytes) than in the cell, GLUT1 generally catalyzes the net import of glucose from the extracellular medium into the cell. Under this condition, Vmax is achieved at high external glucose concentrations.

Like other uniporters, GLUT1 alternates between two conformational states: in one, a glucose-binding site faces the outside of the membrane; in the other, a glucose-binding site faces the inside. Figure 7-4 depicts the sequence of events occurring during the unidirectional transport of glucose from the cell exterior inward to the cytosol. GLUT1 also can catalyze the net export of glucose from the cytosol to the extra cellular medium exterior when the glucose concentration is higher inside the cell than outside.

The kinetics of the unidirectional transport of glucose from the outside of a cell inward via GLUT1 can be described by the same type of equation used to describe a simple enzyme-catalyzed chemical reaction. For simplicity, let's assume that the substrate glucose, S, is present initially only on the outside of the membrane. In this case, we can write:

Snnt + GLUT1

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