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- Suppose that in the formation of phenylalanine hydroxylase mRNA, the exons of the pre-mRNA fail to splice together properly and the resulting enzyme is nonfunctional. This produces an accumulation of high levels of phenylalanine and other compounds, which causes neurological damage. What phenotype would be produced in the affected individual?What is meant by intrinsic GTPase activity? Exchange of GDP for GTP on the a-subunit of the G protein Inhibition of GBCR receptor activity Activation of Adenylyl Cyclades Breakdown of cAMP by phosphodiesterase Spontaneous hydrolysis of GTP on the a-subunit of the G-proteinSignal-transducing heterotrimeric G proteins consist of three subunits designated α, β, and γ. The Gα subunit is a GTPase switch protein that cycles between active and inactive states depending on whether it is bound to GTP or to GDP. Review the steps for ligand-induced activation of effector proteins mediated by the heterotrimeric G proteins. Suppose that you have isolated a mutant Gα subunit that has an increased GTPase activity. What effect would this mutation have on the G protein and the effector protein?
- Mutation in the fibroblast growth factor receptor (FGFR) gene results in achondroplasia (dwarfism), which is a dominant condition caused by a single base substitution (GGG>AGG) that changes the amino acid glycine at position 480 to arginine (G480R) in the FGFR protein. FGFR is normally active when FGF binds to it, but the mutant FGFR is always on to stimulate signaling that inhibits excessive bone growth. How can gene therapy be used to treat achondroplasia? Select all that apply. RNAi that knocks down the mutant FGFR expression Adeno-associated viral (AAV) vector that carries the wild-type FGFR Retroviral vector that carries the wild-type FGFR CRISPR with the wild-type FGFR donor DNASome strains of bacteria or microorganisms have developed toxins that can modify the activity of the alpha subunit of G proteins which results in disease. For ex. cholera toxin, produced by Vibrio cholerae, causes ADP ribosylation of the stimulatory Gαs subunit of G proteins. This modification abolishes the GTPase of Gαs, and results in an αs subunit that is always in the “on” or active state. It results in continuous stimulation of adenylyl cyclase (AC). The main cells affected by this are the epithelial cell in gastrointestinal tract. Knowing this altered activity of AC, explain why patients affected by this toxin experience severe diarrhea and dehydration that may result in death.Stimulation of map kinase can help regulate cell division and cell mass. the following effects of map kinase activation explains an increase in cell mass. Phosphorylation of RSK (kinase and the subsequent phosphorylation of S6 ribosomal subunit. Phosphorylation of myosin light chain Phosphorylation of glyceraldehyde dehydrogenase phosphorylation of histone H1 none of these
- In studies trying to understand the regulation of hormone-sensitive adenylatecyclase, it was discovered that non-hydrolyzable GTP analogs and cholera toxin (that inhibits theGTPase activity of Gs ) were able to activate the enzyme in a sustained (irreversible) profile, thereforeindicating that GTP hydrolysis represents a deactivation (turn-off) regulatory step.a) Will these analogs or toxin have any effect on adenylate cyclase activity in the absenceof any added hormone?b) If you add an factor that increases the rate of GTPase hydrolysis of the Gs protein, willthis activate or inhibit the observed downstream effect upon addition of the hormone (this is in theabsence of GTP analogs or toxin). Explain your answer.Which of the following best describes the use of 2-deoxyglucose in allowing for cancer therapy? Elevates p53 levels directly to regulate glycolytic flux Blocks activation of HIF1transcriptional activation Diminishes lactate production by inhibiting lactate dehydrogenase to allow increased levels of pyruvate to force the transport of pyruvate into the matrix and the function of the TCA cycle Diminishes lactate export from the cell to allow increased levels of pyruvate to force the transport of pyruvate into the matrix and the function of the TCA cycle Competes with glucose for hexokinase, allowing inhibition of glycolytic flux, reducing ATP production.GC (Glycocorticoids) binds to the glucocorticoid receptor (GR), which leads to the transcription of a series of genes (PC, PCK1, FBP1, PFKFB1, G6PC and G6P transporter (SLC37A4)) involved in gluconeogenesis. What type of receptor is GR? Where would you expect the activated GR to be located to enhance the expression of the gluconeogenic genes? Which cis-acting elements are used by GR as an activator to turn gene transcription “on”?
- A current focus of molecular medicine is to trigger or promote apoptosis of specific cells. several components of the apoptotic pathways are being targeted using this approach. for following, state specifically how the treatment would be expected to stimulate or inhibit apoptosis. c. Treatment of cells with organic compounds that enter the cell and bind with high affinity to the active site of Caspase-3The ras protein is a mutated G protein that lacks GTPase activity. How does the absence of this activity affect the adenylyl cyclase pathway?Tumor cells from a person with leukemia have been analyzed to determine which oncogene is involved in the transformation. After partial sequencing of the gene, the predicted gene product is identified as a tyrosine kinase. Which of the following proteins would most likely be encoded by an oncogene and exhibit tyrosine kinase activity? A. Nuclear transcriptional activator B. Epidermal growth factor C. Membrane-associated G protein D. Platelet-derived growth factor E. Growth factor receptor