Passage
Diabetic nephropathy (kidney disease) is characterized in part by a significant decrease in the glomerular filtration rate. Podocytes are differentiated cells that surround the glomerular capillaries and counteract the pressure of blood filtration. Hyperglycemia (elevated blood glucose) and capillary hypertension (high blood pressure) , both of which are common in diabetic patients, can subject podocytes to mechanical stress. This mechanical stress has been shown to regulate glucose uptake by podocytes, possibly by altering the production of glucose transport (GLUT) proteins.Researchers investigating GLUT2 and GLUT4 expression in rat podocytes measured the impact of mechanical stress on glucose uptake. Cells were grown for 4 hours on membranes exposed to atmospheric (atm) or high air pressure (HP) to mimic mechanical stress. Antibodies specific to GLUT2 and GLUT4 were used to visualize the expression of each under normal glucose (NG) and hyperglycemic (HG) conditions, and to assess the effect of mechanical stress on expression. The uptake of a radiolabeled glucose analogue, [³H]-2-deoxy-D-glucose (3H-2DG) , was then determined. The quantity of 3H-2DG transported by each GLUT protein was directly proportional to the cell surface expression.
Figure 1 Cell surface expression of GLUT transporters in response to mechanical stress and varying glucose concentration.In vivo studies have shown that transport via GLUT2 is noninducible and depends only on extracellular glucose concentrations. However, GLUT4-mediated uptake is induced by insulin binding and occurs under high glucose conditions when insulin is released. The standard K_m values for GLUT2 and GLUT4 are 19.4 and 4.3 mM, respectively, at normal blood glucose levels after a meal (~7.8 mM) . The data shown in Figure 2 represent the combined kinetic properties of both transporters.
Figure 2 Plot of glucose uptake in podocytes with and without mechanical stress.
Adapted from Lewko, B., Bryl, E., Witkowski, J. M., Latawiec, E., Angielski, S., & Stepinski, J. (2005) . Mechanical stress and glucose concentration modulate glucose transport in cultured rat podocytes. Nephrology Dialysis Transplantation, 20(2) , 306-311.
-Which statement about glucose transport under physiological conditions is consistent with the kinetic data provided in the passage?

Question

Passage
Diabetic nephropathy (kidney disease) is characterized in part by a significant decrease in the glomerular filtration rate. Podocytes are differentiated cells that surround the glomerular capillaries and counteract the pressure of blood filtration. Hyperglycemia (elevated blood glucose) and capillary hypertension (high blood pressure) , both of which are common in diabetic patients, can subject podocytes to mechanical stress. This mechanical stress has been shown to regulate glucose uptake by podocytes, possibly by altering the production of glucose transport (GLUT) proteins.Researchers investigating GLUT2 and GLUT4 expression in rat podocytes measured the impact of mechanical stress on glucose uptake. Cells were grown for 4 hours on membranes exposed to atmospheric (atm) or high air pressure (HP) to mimic mechanical stress. Antibodies specific to GLUT2 and GLUT4 were used to visualize the expression of each under normal glucose (NG) and hyperglycemic (HG) conditions, and to assess the effect of mechanical stress on expression. The uptake of a radiolabeled glucose analogue, [³H]-2-deoxy-D-glucose (3H-2DG) , was then determined. The quantity of 3H-2DG transported by each GLUT protein was directly proportional to the cell surface expression.

Figure 1 Cell surface expression of GLUT transporters in response to mechanical stress and varying glucose concentration.In vivo studies have shown that transport via GLUT2 is noninducible and depends only on extracellular glucose concentrations. However, GLUT4-mediated uptake is induced by insulin binding and occurs under high glucose conditions when insulin is released. The standard K_m values for GLUT2 and GLUT4 are 19.4 and 4.3 mM, respectively, at normal blood glucose levels after a meal (~7.8 mM) . The data shown in Figure 2 represent the combined kinetic properties of both transporters.

Figure 2 Plot of glucose uptake in podocytes with and without mechanical stress.
Adapted from Lewko, B., Bryl, E., Witkowski, J. M., Latawiec, E., Angielski, S., & Stepinski, J. (2005) . Mechanical stress and glucose concentration modulate glucose transport in cultured rat podocytes. Nephrology Dialysis Transplantation, 20(2) , 306-311.
-Which statement about glucose transport under physiological conditions is consistent with the kinetic data provided in the passage?

Quizplus · Accepted Answer

11ecba2d_0e82_5607_a3bf_6fe1ab303083_MD0008_00 Rate laws are experimentally determined equations that express a reaction rate in terms of the concentrations of reactants. Most simple biochemical processes and enzymatic reactions have rate laws that can be classified as either zero or first-order. For zero-order reactions, the rate is independent of the substrate concentration because there is an excess of substrate and a limited amount of enzyme. The rate is only dependent on the enzyme concentration and activity, which is represented by the rate constant. In contrast, the reaction rate is dependent on substrate concentration in a first-order process. The K_m value represents the substrate concentration at which half of an enzyme's active sites are filled and can be used to predict the reaction order of a rate law. When K_m is higher than the substrate concentration, active sites in the enzyme are available and the reaction behaves like a first-order process that is dependent on substrate concentration. However, if the K_m is substantially lower than the substrate concentration, the active sites are saturated and the reaction resembles a zero-order process. GLUT transporters under physiological conditions are exposed to a glucose concentration of approximately 7.8 mM/L after a meal. The passage states that GLUT2 transport is dependent on extracellular glucose concentration, and the K_m value of 19.4 is much greater than 7.8 mM. Under these conditions, GLUT2-mediated uptake is a typical first-order process. (Choice B) Glucose uptake occurs via passive transport, which does not require ATP. (Choice C) According to the passage, the normal glucose concentration in the fed state is ~7.8 mM. This is substantially higher than the K_m value (4.3 mM) of GLUT4, which indicates that under these conditions GLUT4 is approaching saturation and glucose concentration is not a limiting factor. (Choice D) Glucose enters cells down a concentration gradient through the GLUT transporters. Educational objective: Enzymatic reactions are typically zero-order or first-order reactions. In zero-order reactions the rate is only dependent on the rate constant because substrate concentrations exceed the K_m. First-order reactions depend on substrate concentration and occur when the K_m is greater than the substrate concentration.

Passage Diabetic Nephropathy (Kidney Disease) Is Characterized in Part by a a Significant