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1. Nearly 500 million people in the world are estimated to have diabetes mellitus, metabolic disorders that share the hallmark of elevated blood Diabetic state Pancreas -B-cell a-cell glucose levels that persist over long periods of time. Type 1 diabetes is caused by a loss of insulin- producing cells in the pancreas, while Type 2 diabetes is associated primarily with insulin resistance, meaning that insulin is produced, but the body is insensitive to it and cells unable to efficiently take up glucose from the blood stream. In addition to reducing uptake of glucose in peripheral tissues, reduced insulin production or increased insulin resistance are trigger the liver to activate glucose production by gluconeogenesis, further increasing blood glucose levels and exacerbating the disease. As such, a frontline treatment for Type 2 diabetes is the drug metformin, which acts indirectly to inhibit gluconeogenesis in the liver. You are a research biochemist who would like to develop new drugs that act to directly inhibit gluconeogenesis. You have just gained access to a library of thousands of small molecules of unknown activity, and you would like to identify lead compounds that have specific inhibitory activity against steps in the gluconeogenesis pathway. L Insulin LInsulin TGlucagon Glucose; ↑ Glucose Peripheral tissues TGluconeogenesis ↑ Glycogenolysis Liver (a) What additional steps and enzymes are required in liver cells but are unnecessary in your in vitro reconstitution?

1. Nearly 500 million people in the world are estimated to have diabetes mellitus, metabolic disorders that share the hallmark of elevated blood Diabetic state Pancreas -B-cell a-cell glucose levels that persist over long periods of time. Type 1 diabetes is caused by a loss of insulin- producing cells in the pancreas, while Type 2 diabetes is associated primarily with insulin resistance, meaning that insulin is produced, but the body is insensitive to it and cells unable to efficiently take up glucose from the blood stream. In addition to reducing uptake of glucose in peripheral tissues, reduced insulin production or increased insulin resistance are trigger the liver to activate glucose production by gluconeogenesis, further increasing blood glucose levels and exacerbating the disease. As such, a frontline treatment for Type 2 diabetes is the drug metformin, which acts indirectly to inhibit gluconeogenesis in the liver. You are a research biochemist who would like to develop new drugs that act to directly inhibit gluconeogenesis. You have just gained access to a library of thousands of small molecules of unknown activity, and you would like to identify lead compounds that have specific inhibitory activity against steps in the gluconeogenesis pathway. L Insulin LInsulin TGlucagon Glucose; ↑ Glucose Peripheral tissues TGluconeogenesis ↑ Glycogenolysis Liver (a) What additional steps and enzymes are required in liver cells but are unnecessary in your in vitro reconstitution?

Biochemistry
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
Problem 1P
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1. Nearly 500 million people in the world are Diabetic state estimated to have diabetes mellitus, metabolic disorders that share the hallmark of elevated blood Pancreas B-cell a-cell glucose levels that persist over long periods of time. Type 1 diabetes is caused by a loss of insulin- producing cells in the pancreas, while Type 2 diabetes is associated primarily with insulin resistance, meaning that insulin is produced, but the body is insensitive to it and cells unable to efficiently take up glucose from the blood stream. In addition to reducing uptake of glucose in peripheral tissues, reduced insulin production or increased insulin resistance are trigger the liver to activate glucose production by gluconeogenesis, further increasing blood glucose levels and exacerbating the disease. As such, a frontline treatment for Type 2 diabetes is the drug metformin, which acts indirectly to inhibit gluconeogenesis in the liver. You are a research biochemist who would like to develop new drugs that act to directly inhibit gluconeogenesis. You have just gained access to a library of thousands of small molecules of unknown activity, and you would like to identify lead compounds that have specific inhibitory activity against steps in the gluconeogenesis pathway. I Insulin IInsulin ↑ Glucagon ↑Glucose Peripheral tissues Glucose TGluconeogenesis 1 Glycogenolysis Liver (a) What additional steps and enzymes are required in liver cells but are unnecessary in your in vitro reconstitution? (b) Your screen resulted in two lead compounds that are reversible inhibitors of each reaction. You determined that the lead compound 1 is a competitive inhibitor of the first reaction in the bypass, while lead compound 2 is a noncompetitive inhibitor of the last reaction in the bypass and you now need to determine if they are competitive or noncompetitive inhibitors. Draw the curves for the velocity of each reaction as a function of substrate concentration in the presence of each inhibitor on the graphs below. Label the x-axis of each graph (no need to indicate units).
Transcribed Image Text:1. Nearly 500 million people in the world are Diabetic state estimated to have diabetes mellitus, metabolic disorders that share the hallmark of elevated blood Pancreas B-cell a-cell glucose levels that persist over long periods of time. Type 1 diabetes is caused by a loss of insulin- producing cells in the pancreas, while Type 2 diabetes is associated primarily with insulin resistance, meaning that insulin is produced, but the body is insensitive to it and cells unable to efficiently take up glucose from the blood stream. In addition to reducing uptake of glucose in peripheral tissues, reduced insulin production or increased insulin resistance are trigger the liver to activate glucose production by gluconeogenesis, further increasing blood glucose levels and exacerbating the disease. As such, a frontline treatment for Type 2 diabetes is the drug metformin, which acts indirectly to inhibit gluconeogenesis in the liver. You are a research biochemist who would like to develop new drugs that act to directly inhibit gluconeogenesis. You have just gained access to a library of thousands of small molecules of unknown activity, and you would like to identify lead compounds that have specific inhibitory activity against steps in the gluconeogenesis pathway. I Insulin IInsulin ↑ Glucagon ↑Glucose Peripheral tissues Glucose TGluconeogenesis 1 Glycogenolysis Liver (a) What additional steps and enzymes are required in liver cells but are unnecessary in your in vitro reconstitution? (b) Your screen resulted in two lead compounds that are reversible inhibitors of each reaction. You determined that the lead compound 1 is a competitive inhibitor of the first reaction in the bypass, while lead compound 2 is a noncompetitive inhibitor of the last reaction in the bypass and you now need to determine if they are competitive or noncompetitive inhibitors. Draw the curves for the velocity of each reaction as a function of substrate concentration in the presence of each inhibitor on the graphs below. Label the x-axis of each graph (no need to indicate units).
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