1. Polycystic kidney disease (PKD) is an inherited disease that causes water loss from the body and affects cell division in the kidneys. Because water movement across cell membranes is related to ion movement, scientists investigated the role of the Na+ /K+ ATPase (also known as the sodium/potassium pump) in this disease. Ouabain, a steroid hormone, binds to the Na+ /K+ ATPase in plasma membranes. Individuals with PKD have a genetic mutation that results in an increased binding of ouabain to the Na+ /K+ ATPase. The scientists treated normal human kidney (NHK) cells and PKD cells with increasing concentrations of ouabain and measured the number of cells (Figure 1) and the activity of the Na+ /K+ ATPase (Figure 2) after a period of time. The scientists hypothesized that a signal transduction pathway that includes the protein kinases MEK and ERK (Figure 3) may play a role in PKD symptoms.
Figure 3. Signal transduction pathway hypothesized to play a role in the increased number of PKD cells
(a) Describe the characteristics of the plasma membrane that prevent simple diffusion of Na+ and K+ across the membrane. Explain why ATP is required for the activity of the Na+ / K+ ATPase. (b) Identify a dependent variable in the experiment represented in Figure 1. Justify the use of normal human kidney (NHK) cells as a control in the experiments. Justify the use of a range of ouabain concentrations in the experiment represented in Figure 1. (c) Based on the data shown in Figure 2, describe the relationship between the concentration of ouabain and the Na+ /K+ ATPase activity both in normal human kidney (NHK) cells AND in PKD cells. The scientists determined that Na+ / K+ ATPase activity in PKD cells treated with 1 pM ouabain is 150 units of ATP hydrolyzed/sec. Calculate the expected Na+ / K+ ATPase activity (units/sec) in PKD cells treated with 6 10 pM ouabain. (d) In a third experiment, the scientists added an inhibitor of phosphorylated MEK (pMEK) to the PKD cells exposed to 4 10 pM ouabain. Based on Figure 3, predict the change in the relative ratio of ERK to pERK in ouabain-treated PKD cells with the inhibitor compared with ouabain-treated PKD cells without the inhibitor. Provide reasoning to justify your prediction. Using the data in Figure 1 AND the signal transduction pathway represented in Figure 3, explain how the concentration of cyclin proteins may increase in PKD cells treated with 4 10 pM ouabain.
2. Geneticists investigated the mode of inheritance of a rare disorder that alters glucose metabolism and first shows symptoms in adulthood. The geneticists studied a family in which some individuals of generations II and III are known to have the disorder. Based on the pedigree (Figure 1), the geneticists concluded that the disorder arose in individual II−2 and was caused by a mutation in mitochondrial DNA.
(a) The disorder alters glucose metabolism. Describe the atoms AND types of bonds in a glucose molecule.
(b) Using the template in the space provided for your response, construct an appropriately labeled graph based on the data in Table 1. Determine one individual who is both at risk of developing the disorder and has a significantly different blood glucose level from that of individual IV−1.
(c) Based on the pedigree, identify all individuals in generation IV who can pass on the mutation to their children.
(d) Based on the fact that individual II−2 is affected, a student claims that the disorder is inherited in an X-linked recessive pattern. Based on the student’s claim, predict which individuals of generation III will be affected by the disorder. Based on the pedigree, justify why the data do NOT support the student’s claim.