Interactive
Quiz on
Krebs Cycle
Reading:
Textbook Reading: Biochemistry, 3rd Edition, by Voet & Voet, Chapter 21.
Some recent articles
(optional reading):
L. J. Reed (2001) "A trail of research from lipoic acid to a-keto
acid dehydrogenase complexes," J. Biol. Chem. 276: 38329-38336.
T. E. Roche, Y. Hiromasa, A. Turkan, X. Gong, T. Peng, X. Yan, S. A. Kasten, H.
Bao & J. Dong (2003) "Essential roles of lipoyl domains in the activated
function and control of pyruvate dehydrogenase kinases and phosphatase isoform
1," Eur. J. Biochem. 270: 1050-1056.
R. A. Harris, M. M. Bowker-Kinley, B. Hyang & P. Wu (2002) "Regulation of the
activity of the pyruvate dehydrogenase complex," Advan. Enzyme Regul. 42: 249-259.
T. E. Roche, Y. Hiromasa, A. Turkan, X. Gong, T. Peng, X. Yan, S. A. Kasten, H.
Bao & J. Dong (2003) "Essential roles of lipoyl domains in the activated
function and control of pyruvate dehydrogenase kinases and phosphatase isoform
1," Eur. J. Biochem. 270: 1050-1056.
H.-S. Kwon & R. A. Harris (2004) "Mechanisms responsible for regulation of
pyruvate dehydrogenase kinase 4 gene expression," Advan. Enzyme Regul. 44:
109-121.
V. I. Bunik (2003) "2-Oxo acid dehydrogenase complexes in redox regulation: Role
of the lipoate residues and thioredoxin," Eur. J. Biochem. 270: 1036-1042.
S. J. Lloyd, H. Lauble, G. S. Prasad & C. D. Stout (1999) "The
mechanism of aconitase: 1.8 A resolution crystal structure of the S642A:citrate
complex," Protein Science 8: 2655-2662.
C. R. D. Lancaster (2002) "Succinate:quinone oxidoreductases: an overview,"
Biochimica et Biophysica Acta 1553: 1-6.
G. Cecchini (2003) "Function and structure of complex II of the respiratory
chain," Annu. Rev. Biochem. 72: 77-109.
O. E. Owen, S. C. Kalhan & R. W. Hanson (2002) "The key role of anaplerosis and
cataplerosis for citric acid cycle function," J. Biol. Chem. 277: 30409-30412.
J. L. S. Milne, X. Wu, M. J. Borgnia, J. S. Lengyel, B. R. Brooks, D. Shi, R. N.
Perham & S. Subramaniam (2006) "Molecular structure of a 9-MDa icosahedral
pyruvate dehydrogenase subcomplex containing the E2 and E3 enzymes using
cryoelectron microscopy," J. Biol. Chem. 281: 4364-4370.
C. A. Brautigam, R. M. Wynn, J. L. Chuang, M. Machius, D. R. Tomchick & D. T.
Chuang (2006) "Structural insight into interactions between dihydrolipoamide
dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase
complex," Structure 14: 611-621.
Potential Test Questions:
1. Diagram the Krebs Citric Acid Cycle, beginning with pyruvate, giving structures and names of all enzyme substrates and products and names of enzymes (no abbreviations). Include on your diagram where NAD+ ® NADH, FAD ® FADH2 (coenzyme Q ® QH2), or GDP + Pi ® GTP, and where coenzyme A, H2O, or CO2 are substrates or products of reactions.
2. Describe the sequence of reactions catalyzed by the Pyruvate Dehydrogenase enzyme complex. Provide a diagram showing structures of the relevant portions of major intermediates at each step. Include the role of each of the various cofactors and prosthetic groups of E1, E2, and E3. What is the nature and the role of the "long swinging arm" that includes lipoamide and its attachment to the complex?
Group Presentations
On Thursday or Friday November
13 or 14 (depending on the section), each group of 3-4 students will
make a 5 minute presentation on an assigned enzyme in
the Krebs Citric Acid Cycle or a related topic. For each enzyme, the reaction
mechanism should be briefly presented, along with any relevant information about
enzyme structure, energetics, inhibitors, regulation, etc. At least one short
answer question, suitable for including in a tutorial, should be posed to the
class at the end of the presentation.
Students should
minimally research material in Chapter 21 of the textbook and the interactive
module embedded in the class notes. Additional information for some topics may
be found in recent articles listed above (optional reading) or in other chapters
of the textbook (e.g., 22 & 23). Advance preparation is
expected.
The
presentation, to be graded on a scale of one to five, will count as five points
of the last quiz. In addition, there will be a small prize for best presentation.
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Krebs Cycle: Enzyme or Topic |
Students: Section 1 |
Students: Section 2 | Students: Section 3 |
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Citrate Synthase |
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Aconitase |
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Isocitrate Dehydrogenase |
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a-Ketoglutarate Dehydrogenase |
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Succinyl CoA Synthetase |
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Succinate Dehydrogenase |
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Fumarase |
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Malate Dehydrogenase |
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| Stereospecificity of reactions; tracing labeled atoms through Krebs Cycle. | |||
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Net Inputs and Outputs; Relation to Other Pathways |
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| Summary of Regulation of Citric Acid Cycle |
Copyright © 1998-2007 by Joyce J. Diwan. All rights reserved.
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Interactive
Quiz on |