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- 5. (a) Hexokinase IV is known as glucokinase (GCK) and is a central metabolic enzyme that participates in glucose homeostatic maintenance by governing the rates of glucose catabolism in pan- creatic B-cells and glycogen storage in hepatocytes (liver cells). In contrast to the regulatory mecha- nisms of hexokinase I or Il in other tissues, GCk is regulated by binding to the Glucokinase Regulatory Protein (GRP) located in the cell nucleus. When glucose in hepatocytes is low, GCK is sequestered in the nucleus by binding to the GRP. High glucose, for instance, after ingestion of a meal, disrupts the GRP-GCK complex, allowing the GCK to diffuse into the cytoplasm to convert glucose into glucose-6- phosphate. Contrast the properties of hexokinases I and IV with respect to oligomeric structure, mech- anism of regulation of their activity, KM value, and dependence of catalytic activity on cellular location. Hexokinase l is found in, for instance, muscle tissue. Property subunit structutre…5. (a) Hexokinase IV is known as glucokinase (GCK) and is a central metabolic enzyme that participates in glucose homeostatic maintenance by governing the rates of glucose catabolism in pan- creatic B-cells and glycogen storage in hepatocytes (liver cells). In contrast to the regulatory mecha- nisms of hexokinase I or Il in other tissues, GCK is regulated by binding to the Glucokinase Regulatory Protein (GRP) located in the cell nucleus. When glucose in hepatocytes is low, GCK is sequestered in the nucleus by binding to the GRP. High glucose, for instance, after ingestion of a meal, disrupts the GRP-GCK complex, allowing the GCK to diffuse into the cytoplasm to convert glucose into glucose-6- phosphate. Contrast the properties of hexokinases I and IV with respect to oligomeric structure, mech- anism of regulation of their activity, KM value, and dependence of catalytic activity on cellular location. Hexokinase I is found in, for instance, muscle tissue. Property subunit structutre…Can anyone suggest a way of increasing phosphorylation of IKK alpha (Ser176/180)? Any potent phosphatase inhibitor in combination with TNF alpha?
- In 1994, the U.S. Public Health Service identified “10 Essential Public Health Services.” For each of the ten, briefly describe a specific activity that has been used in the response to COVID-19.The progressive loss of cardiac myocytes due to cell death has been associated with cardiac dysfunction and heart failure. Which of the following would lead to a significant loss of cardiac myocytes? Select all that apply Treatment of rapamycin which results in inhibition of mTOR activity Prolonged or severe ER stress with increased accumulation of unfolded proteins Activation of AMPK and phosphorylation of the TSC1 complex mTOR activation and phosphorylation of Ulk114) Which of the following correctly ranks the steps in the secretory pathway? 1. Active PKA subunits phosphorylate targets in the cell, regulating function. 2. The catalytic subunits of PKA dissociate. 3. Gprotein a subunit exchanges bound GDP for GTP. 4. CAMP binds to the regulatory subunits of PKA, activating it. 5. Ga subunit dissociates from complex and activates adenylate cyclase. 6. Ligand (hormone) binds to receptor. 7. Activated adenylate cyclase produces CAMP from ATP.
- 1.Describe in detail the signal transduction pathway that leads to activation of either PKA, Kinase or PC. 2. Describe in detail the signal transduction pathway that leads to activation of MAPKinase or Akt/PKB. 3.Describe the similarities and differences in the structures of GPCRs specific for various ligands including the extracellular , transmembrane , and intracellular domains.The MARCH-1 E3-ubiquitin ligase is expressed in B cells, dendritic cells, and macrophages. The pathway regulated by MARCH-1 is targeted by some pathogens in an immune evasion strategy. In this strategy, the pathogens encode: A protein that induces degradation of MARCH-1 A protein that mimics MARCH-1 and functions similarly A protein that binds to MARCH-1 and inhibits its function A protein that is induced by IL-10 in macrophages and dendritic cells A protein that induces degradation of CD861. Which of the following signaling events is NOT engaged downstream of phospholipase C (PLC)-gamma activation? a. Calcium ion (Ca2+) release from the endoplasmic reticulum (ER) b. Heterodimerization of the subunits c-Fos and c-Jun to form the transcription factor AP-1 c. IkappaB degradation and resulting translocation of NFkappaB into the nucleus d. Recruitment of protein kinase C (PKC)-theta to the plasma membrane e. PIP3 generation at the plasma membrane which recruits and activates Akt, leading to cytoskeletal remodeling
- A biotech company develops a biosensor that measures the presence of proteins activated by growth factor signaling cascades. Which binding domain would you use to each of the following activation peptides or signaling molecules. Phosphotyrosine A. SH2 Domain A peptide with the sequence Arg-Ala-Pro-Pro-Leu- B. Bromodomain Pro C. 14-3-3 Domain ◆ Phosphatidyl inositol Triphosphate (PIP3) Phosphoserine Acetylated Lysine D.PH Domain E. SH3 DomainThe number of calories used during physical exercise is greater than the number of calories used for the movements themselves. This may be caused in part by exercise-induced expression of uncoupling protein 1 (UCP1) in subcutaneous fat. Subcutaneous fat is mostly white fat cells but can also contain brown fat cells in mice and humans. As part of a thermogenesis program, UCP1 directly reduces the proton gradient driving oxidative phosphorylation. UCP1 expression is a characteristic of brown fat cells only and is induced by the protein irisin. The data in Table 1 address the relationship between exercise and: • expression of UCP1 in subcutaneous fat cells, • expression of FNDC5 (a transmembrane protein in skeletal muscle plasma membranes), • blood levels of irisin (a soluble protein formed by cleaving the extracellular domain of FNDC5), and • expression of adiponectin (a hormone produced by white fat cells) in both wild-type mice and mice with overexpression skeletal muscle PGC-1a (a…Which phenomenon is not readily explained by the 'induced-fit' hypothesis, that is readily explained by the 'fluctuation-fit hypothesis? Catalysis by optimal interaction with the transition state of substrates. O Specificity of enzymes for substrates. O Lower binding affinity for products, enabling their release once chemistry has happened. O Cooperativity of binding to the remaining 3 sites of hemoglobin when oxygen binds to the first of the four sites.
