BME365R.2022.HW2.revisedquestions

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1 BME 365R: Engineering Physiology I Fall 2022 HOMEWORK 2 Use this space to list your collaborators and which question #’s you worked on together. This assignment includes links to additional required reading so plan your time appropriately. Firstname Lastname (Question #)

2 1. Cell Membranes A 5-year-old child presents with a history of recurrent bacterial infections. During each infection, there is an appropriate increase in his total white cell count (including neutrophils), but his biopsies show very few neutrophils at the sites of infection. You suspect that this patient suffers from a rare genetic disorder called leukocyte adhesion deficiency, caused by a mutation in the gene ITGB2 . This gene encodes a subunit of the β2 – integrin protein. A. Where are functional integrin proteins located in mammalian cells? (2 point) B. Integrins assemble into heterodimers, each consisting of one alpha and one beta subunit. What level of protein structure does this represent? (2 points) C. Among patients with leukocyte adhesion deficiency, mutations in ITGB2 fall into two main categories. Class 1 mutations are deletions and insertions in the ITGB2 sequence while Class 2 mutations are missense mutations. How do you expect the protein levels of ITGB2 to differ in Class 1 versus Class 2 patients? (6 points) D. How would a missense mutation in the β2 – integrin ectodomain impact function of the integrin? In the endodomain? (6 points)

3 2.Cystic Fibrosis Mary is a 19 year old woman who has been diagnosed with this genetic disease. Her past laboratory findings include a positive sweat test and an elevated concentration of chloride ions. She frequently suffers from bacterial infections and digestive ailments. Over time, Mary’s lung function has reduced to 28% of normal. A. To measure lung dysfunction, it is first necessary to establish values for normal lung function. Often we may not be aware of the underlying factors that were part of the decisions in setting these values. Read the following 2 brief commentaries and explain how the values for normal lung function were determined in each study. How might this impact clinical care? (3-4 sentences each, 10 points each) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631137/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136072/ B. CF is primarily caused by one of several DNA mutations. What protein is affected by the mutation? Describe the normal function and location in the cell of this protein. (5 points) C. How do the different mutations in the gene affect the structure of the protein? (suggest at least two mechanisms) (5 points)

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4 3. Electron Transport and Cellular Respiration In March 2006, 28 Providence firefighters were admitted to hospitals after fighting three fires in local residences and businesses. None had suffered burns, but smoke inhalation had caused moderate to severe symptoms among the group that included headache, dizziness, heart attack and apparent confusion. While carbon monoxide (CO) has long been known to be produced during combustion of a variety of materials, the burning of modern plastics (as well as several natural products) produces hydrogen cyanide (HCN). CO exerts it primary effects by binding with high affinity to hemoglobin. Hemoglobin (Hb) binds O 2 reversibly, and releases O 2 (e.g. at active tissues) depending on (among other factors) the PO 2 . Another factor that influences the ability of Hb to release O 2 is pH. Hydrogen ions can bind to Hb and cause a decrease in the affinity of Hb for O 2 . Thus, at low pH, the “unloading” of O 2 by Hb is facilitated. HCN exerts its effects by acting as an inhibitor of cytochrome oxidase in the inner mitochondrial membrane. HCN does not directly interfere with the ability of hemoglobin to carry O 2 in the blood, but it does block electrons from being transferred to the final electron acceptor of our ETC (O 2 ). This means that O 2 is not being reduced to H 2 O, and remains in its oxidized form, even in active body tissues. In fact, because cells are not consuming O 2 , the concentration gradient between cells and arterial blood is essentially eliminated, such that hemoglobin retains its bound O 2 . A. What is the impact of HCN on cellular ATP production? Explain your answer. (3 points) B. What do you predict the effect of CO poisoning to be on aerobic cellular respiration? Explain your answer. (3 points) C. How can changes in blood pH help you diagnose a problem with aerobic cellular respiration? (4 points) Fires can expose unprotected firefighters to both CO and HCN and it is imperative to distinguish between these exposures in order to provide adequate treatment. One of the challenges in making the correct diagnosis is that many of the symptoms of each are somewhat nonspecific and overlapping. While it is possible to carry out blood tests to measure the level of cyanide, many hospitals are not able to carry out this test rapidly in their own laboratories. This means physicians must make a probable diagnosis based on other information.

5 CO poisoning can be treated with hyperbaric O 2 (exposing patients to high levels of O2 at elevated pressures). HCN poisoning can be treated with nitrites that bind to hemoglobin, creating a form of hemoglobin known as methemoglobin. Methemoglobin binds to HCN with higher affinity than cytochrome oxidase. In the presence of methemoglobin, HCN will preferentially bind to methemoglobin, rather than cytochrome oxidase. One factor to keep in mind however, is that methemoglobin cannot bind to O 2 . D. Do you predict hyperbaric oxygen to be helpful, harmful or “neutral” in cases of HCN poisoning? Explain your answer. (5 points) E. What do you predict will happen if a patient with CO poisoning was given nitrites? Explain your answer. (5 points)

6 Exam Practice: The following questions are the type you can expect to see on exams throughout the semester. (3 points each) 4. Which one of the following is NOT consistent with secondary active transport? (A) The movement of an ion down its concentration gradient is coupled to the movement of another molecule against its concentration gradient. (B) In secondary active transport ATP is hydrolyzed. (C) Cotransport and exchange are variations of secondary active transport. (D) In secondary active transport, the ion that is moving down its concentration gradient is referred to as the driving ion. (E) All of the above are true about secondary active transport. 5. Na+, and K+, Ca2+, and Cl− permeation through their respective ion channels represents an example of: (A) Passive transport (B) Primary active transport (C) Secondary active transport (D) A and C only (E) A, B, and C 6. You are studying a vitamin that is fat-soluble. How will these vitamin molecules enter a mammalian cell? a. they will dissolve in the fat layers of the membrane and enter the cell by diffusion b. they will pass through protein pores in the cell membrane c. they will be absorbed by phagocytosis d. they never enter cells

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