Problem Set 6 Principles of Cell Biology

Problem Set 6Principles of Cell Biology1. Lysosomes are single membrane bound organelles that, by definition, stain positively with acidphosphatase. They play a critical role in the ability of cells to degrade a variety ofmacromolecules.a. Several drugs have been developed by companies like Genzyme (Sanofi) that can givesome relief to a variety of lysosomal enzyme diseases. Why is “replacement enzymetherapy” an appropriate word to use for many of these therapies?b. Chloroquine has been used to disrupt the lysosomes. How does this work and how ischloroquine used today as a drug?c. Hurler’s Syndrome and I Cell disease are both lysosomal storage diseases but they arefundamentally different from each other. How is that the case?d. You are investigating a possible newly discovered and very rare lysosomal storagedisease and need to identify its molecular defect. You hypothesize that the defect (neverbefore seen in any lysosomal storage disease) is a defective M6P receptor. How mightyou use cell culture experiments to investigate this hypothesis?e. Proteasomes were mentioned in class. How does the UPR (Unfolded Protein Response)and ubiquitin relate to the large protein complexes that number 30,000/cell?2. Autophagy was mentioned in class. While we have been aware of the normal function ofautophagy in most cells for decades, it has recently gained interest due to its implications in thetreatment of cancer.a. Describe autophagy and how it differs mechanistically from heterophagy.b. Why would a researcher want to manipulate autophagy in cancer cells?3. Acetylcholine (ACH) is a neurotransmitter that works at the neuromuscular junctions.a. What role does ACH have in the disease Myasthenia Gravis?b. What types of drugs are used to treat Myasthenia Gravis and what is the mode ofaction?4. Mitochondria were once thought to serve only one role – generation of ATP throughchemiosmotic oxidative phosphorylation. Now, however, we recognize that they appear to haveanother role that is being targeted by both the large and small pharmaceutical industries as apossible means to develop an improved paradigm to tackle cancer.a. How is the generation of ATP different in the mitochondria versus in the cytoplasm?b. How does the SGLT pump glucose into the cell and how can it pump glucose from theextracellular environment into the cell against its gradient without the use of ATP?.c. As presented in class, mitochondria appear to play critical roles in cell death. Under eachof the headings below, explain how each of the components is related to mitochondriamediated cell death.i.ii.iii.iv.OligomycinDNP/valinomycinCarbon monoxideMitochondrial permeability transition porev. Bax/Bidvi. Caspasesvii. Cytochrome c5. Energy production is the primary responsibility of the mitochondria.a. Describe the necessary structures and ingredients needed for the mitochondria toproduce ATP in the Citric Acid Cycle.b. What is cyanide? How does cyanide affect the process of oxidative phosphorylation?What would occur to an organism if cyanide is not promptly treated?c. Researchers have developed several techniques for monitoring mitochondrial function,including vital dyes. Name two vital dyes and how each specifically functions. Brieflydesign an experiment which you could use these dyes to monitor mitochondrial activity.6. Chloroplasts are the mitochondria of plants and other organisms that rely on photosynthesis forthe creation of ATP for energy.a. What are the four stages of photosynthesis and give a brief description of each stage?b. Purple bacteria are microorganisms capable of utilizing photosynthesis, but in a mannerdifferent from plants. Describe this difference.c. Describe the differences between carbon fixation and photorespiration. How is Rubiscoinvolved in each?d. Cyanobacteria are now being considered as one of the future approaches to developingrenewable energy sources. What are the advantages of these organisms?e. What is artificial photosynthesis?



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