82. Regulation of cellular metabolism by insulin requires activation of the insulin-receptor substrate protein-1 (IRS1). Some individuals who have type 2 diabetes mellitus have mutations in the IRS1 gene. Which of the following normal steps in insulin signaling is most likely to be impaired by these mutations? A) Cleavage of IRS1 by the insulin receptor B) Phosphorylation of IRS1 by the insulin receptor C) Production of inositol 1,4,5-trisphosphate by IRS1 OD) Stimulation of a G protein by IRS1 E) Synthesis of diacylglycerol by IRS1
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- 5. (а) 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. Hexokinase IV is known as glucokinase (GCK) and is a central metabolic enzyme that Property subunit structutre…. Suggest the effects of each of the following mutations on the physio- logical role of chymotrypsinogen: (a) R15S (b) Cis (c) T147SExplain, why many cancer cells maintain high concentrations of insulin-like growth factors (IGFs) in the microenvironment that surrounds them?
- Select all that is correct. 1) C-peptide is not present in mature insulin. 2) The insulin produced by rDNA technology has C-peptide. 3) The pro-insulin has C-peptide. 4) A-peptide and B-peptide of insulin are interconnected by disulphide bridges.32. During a study of insulin response, a healthy nonobese 24-year-old woman consumes four pancakes with maple syrup and drinks two glasses of apple juice. The insulin released in response to this meal binds to its receptor and activates the insulin receptor tyrosine kinase. Under these conditions, activation of which of the following in the liver is most likely to occur in this subject? A) Glucose transporter-4 (GLUT-4) B) Glycogen phosphorylase C) Glycogen phosphorylase kinase D) Glycogen synthase E) Phosphoenolpyruvate carboxykinaseExplain the function(s) of Hsp90. Name two factors which lead to the increase of this protein in cells.
- 64 An investigator is studying the mechanism of action of an insulin-sensitizing drug. The addition of the drug to cultured mouse hepatocytes is observed, and results show increased phosphorylation and inhibition of acetyl-CoA carboxylase Which of the following processes is most likely inhibited by this action of the drug? A) Fatty acid oxidation B) Fatty acid synthesis C) Glycogen synthesis D) Glycolysis E) Protein synthesis5. (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…
- Why is there a distinction of c2c12 cells with and without insulin?2. Researchers have discovered significant changes in the gene of some protein, which is a substrate for the insulin receptor. What impact on the insulin signal transduction would such changes have? For the answer: a) draw the scheme of insulin signal transduction in the target cell; b) name proteins and enzymes, activated by insulin in the target cells; c) explain the functions of these enzymes.6. A. List all of the ionizable functional groups that are found in insulin when in aqueous solution. List which amino acid residues have these ionizable groups and list all of the pka and pKb values (including the R groups) that are on both polypeptide chains that make up insulin. (see the table at the end of this HW set; note that tyrosine and cysteine both have unusual pka's, since these side groups ionize above the pKR's given to have a negative charge). B. The isoelectric point of insulin is reported to be around 5.3-5.35. Using the method covered in class, estimate the isoelectric point of insulin and compare your answer to the values above. C. For a polypeptide to be soluble in an aqueous solution, is it good to be near the isoelectric point? Why or why not? Notes: a couple of unusual R group's that ionize (cysteine and tyrosine have R groups that have pka values; histidine has a pkb). The table at the end of this homework set (also in the lecture notes) lists the pka's and…