disease. As such, a tron Type 2 diabetes arug 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. (a) Your first approach is to reconstitute the initial set of bypass reactions that convert pyruvate into PEP in order to screen for inhibitors of enzymes specific to gluconeogenesis. Which enzymes do you need to purify, what cofactors and allosteric effectors do they require, and which reactants do you need to add to reconstitute the reactions for the first bypass? Which intermediates and products are generated? (b) What additional steps and enzymes are required in liver cells but are unnecessary in your in vitro reconstitution? (c) 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. 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).
disease. As such, a tron Type 2 diabetes arug 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. (a) Your first approach is to reconstitute the initial set of bypass reactions that convert pyruvate into PEP in order to screen for inhibitors of enzymes specific to gluconeogenesis. Which enzymes do you need to purify, what cofactors and allosteric effectors do they require, and which reactants do you need to add to reconstitute the reactions for the first bypass? Which intermediates and products are generated? (b) What additional steps and enzymes are required in liver cells but are unnecessary in your in vitro reconstitution? (c) 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. 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).
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
Related questions
Question
Expert Solution
This question has been solved!
Explore an expertly crafted, step-by-step solution for a thorough understanding of key concepts.
Step by step
Solved in 5 steps with 11 images
Recommended textbooks for you
Biochemistry
Biochemistry
ISBN:
9781319114671
Author:
Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:
W. H. Freeman
Lehninger Principles of Biochemistry
Biochemistry
ISBN:
9781464126116
Author:
David L. Nelson, Michael M. Cox
Publisher:
W. H. Freeman
Fundamentals of Biochemistry: Life at the Molecul…
Biochemistry
ISBN:
9781118918401
Author:
Donald Voet, Judith G. Voet, Charlotte W. Pratt
Publisher:
WILEY
Biochemistry
Biochemistry
ISBN:
9781319114671
Author:
Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:
W. H. Freeman
Lehninger Principles of Biochemistry
Biochemistry
ISBN:
9781464126116
Author:
David L. Nelson, Michael M. Cox
Publisher:
W. H. Freeman
Fundamentals of Biochemistry: Life at the Molecul…
Biochemistry
ISBN:
9781118918401
Author:
Donald Voet, Judith G. Voet, Charlotte W. Pratt
Publisher:
WILEY
Biochemistry
Biochemistry
ISBN:
9781305961135
Author:
Mary K. Campbell, Shawn O. Farrell, Owen M. McDougal
Publisher:
Cengage Learning
Biochemistry
Biochemistry
ISBN:
9781305577206
Author:
Reginald H. Garrett, Charles M. Grisham
Publisher:
Cengage Learning
Fundamentals of General, Organic, and Biological …
Biochemistry
ISBN:
9780134015187
Author:
John E. McMurry, David S. Ballantine, Carl A. Hoeger, Virginia E. Peterson
Publisher:
PEARSON