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Description: Case connections are short scenarios or puzzles based on the information from the current unit of study. For the20 nM methotrexate A. 5 nM 5 nM methotrexate methotrexate 20 nM methotrexate 0 methotrexate /[dihydrofolate] /[dihydrofolate]Case 2: A researcher was studying red blood cells from a patient homozygous for the sickle cell mutation in the B- globin gen

****TYPED PLEASE. NOT HAND WRITTEN.****************

******TYPED PLEASE. NOT HAND WRITTEN.**************

Description: Case connections are short scenarios or puzzles based on the information from the current unit of study. For the Unit 1 Case Connections assignment, you will choose two of the following four case connection problems and provide detailed written solutions To earn full credit, you will need to describe why your chosen answer is correct while also discussing why the other answers are incorrect. Your assignment will be graded on your logic and accuracy as well as on the clarity and organization of the overall assignment. Submit your written assignment via the digital drop box. Case 1: Methotrexate works as an anticancer drug by competitively inhibiting the enzyme dihydrofolate reductase. A set of experiments was done using 10 nM dihydrofolate reductase, a range of dihydrofolate concentrations (1μΜ-500 μΜ) and 0,5 nM and 20 nM methotrexate. The initial rates of each of these reactions were measured Which of the following figures shows the most likely outcome of these experiments? (Please be sure to discuss why you choose your answer and why the other choices are incorrect)
20 nM methotrexate A. 5 nM 5 nM methotrexate methotrexate 20 nM methotrexate 0 methotrexate /[dihydrofolate] /[dihydrofolate] luM dihydrofolate 50,N dihydrofolate 500 pM dihydrofolate C. dihydrofolate liM dihydrofolate 500/M dihydrofolate l/[methotrexate] I/[methotrexate]
Case 2: A researcher was studying red blood cells from a patient homozygous for the sickle cell mutation in the B- globin gene ( β EGV). She found that increasing the concentration of one of the following chemicals decreased the frequency of sickling by these cells. What chemical is this most likely to be? A. 2,3-Bisphosphoglycerate (BPG) B. Fe2+ C. glucose D. histidine E. O2
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Case 2 :-

The most common hemoglobin of adults is hemoglobin A (Hb^A) . However patients suffering from sickle cell disease are homozygous for the allele coding for the abnormal variant of hemoglobin (Hb^S) due to a missense mutation in the gene encoding the β subunit of hemoglobin. This missense mutation replaces glutamic acid with valine at the sixth position of the β-globin chain.
The absence of a polar amino acid at this position promotes the non-covalent aggregation of hemoglobin in a low-oxygen environment which distorts red blood cells into a sickle shape and decreases their elasticity. Biochemically, the low oxygen environment causes the beta chain of neighboring hemoglobin molecules to hook together, becoming rigid and polymerized. These cells fail to return to their normal shape when oxygen is restored and thus fail to deform as they pass through narrow vessels, leading to blockage in the capillaries.
In vitro studies of deoxygenation and reoxygenation of sickle-cell hemoglobin indicates that the process is reversible. The hemoglobin molecules polymerize and form crystals as oxygen concentration is lowered. But as the oxygen concentration is increased again, hemoglobin molecules can depolymerize and return to their soluble state. This can be written as:

Figure 1. The equilibrium reaction equation relates non-sickled hemoglobin with sickle cell hemoglobin polymers. The discovery of the sickle cell mutation came from isoelectric focusing, a type of electrophoresis that separates complex mixtures of large molecules by applying an electric current. Hemoglobin taken from patients suffering from sickle cell anemia, individuals who were heterozygous for the abnormal variant, and those that did not have the sickle cell allele were subjected to isoelectric focusing,

Lowered O2 Tension Non-sickled Sickle Cell Hb нь polymers Increase O2 Tension

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