Molecular Biochemistry I

Gluconeogenesis

Reading:

Textbook Reading: Biochemistry, 3rd Edition, by Voet & Voet, p. 843-850.

Some recent articles (optional reading): 
L. T. J. Delbaere, A. M. Sudom, L. Prasad, Y. Leduc & H. Goldie (2004) "Structure/function studies of phosphoryl transfer by  phosphenolpyruvate carboxykinase," Biochim. Biophys. Acta 1697: 271-278.
M. A. Magnuson, P. She & M. Shiota (2003) "Gene-altered mice and metabolic flux control," J. Biol. Chem. 278: 32485-32488.
D. Pacheco-Alvarez, R. S. Solorzano-Vargas & A. L. Del Rio (2002) "Biotin in metabolism and its relationship to human disease," Arch. Med. Res. 33: 439-447.
G. van de Werve, A. Lange, C. Newgard, M.-C. Mchin, Y. Li & A. Berteloot (2000) "New lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase system," Eur. J. Biochem. 267: 1533-1549.
E. P. M. Corssmit, J. A. Romijn & H. P. Sauerwein (2001) "Regulation of glucose production with special attention to nonclassical regulatory mechanisms," Metabolism 50: 742-755.
G. Jiang & B. B. Zhang (2003) "Glucagon and regulation of glucose metabolism," Am. J. Physiol. Endocrinol. Metab. 284: E671-E678.
M. H. Rider, L. Bertrand, D. Vertommen, P. A. Michels, G. G. Rousseau & L. Hue (2004) "6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis," Biochem. J. 381: 561-579.
D. A. Okar, C. Wu & A. J. Lange (2004) "Regulation of the regulatory enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase," Advan. Enzyme Regul. 44: 123-154.
G. Mithieux, F. Rajas & A. Gautier-Stein (2004) "A novel role for glucose-6-phosphatase in the small intestine in the control of glucose homeostasis," J. Biol. Chem. 279: 44231-44234.
C. Wu, S. A. Khan, L.-J. Peng & A. J. Lange (2006) "Roles for fructose-2,6-bisphosphate in the control of fuel metabolism: Beyond its allosteric effects on glycolytic and gluconeogenic enzymes," Advan. Enzyme Regul. 46:72-88.
G.P.A. Bongaerts, H.K. van Halteren, C.A.M. Verhagen & D. J. TH. Wagener (2006) "Cancer cachexia demonstrates the energetic impact of gluconeogenesis in human metabolism," Medical Hypotheses 67: 1213-1222.

Potential Test Questions:

1.a. Write out the two sequential reactions catalyzed by Pyruvate Carboxylase, giving names and structures of reactants and products, including the active site prosthetic group. What is the nature and significance of the linkage of the prosthetic group to the Pyruvate Carboxylase enzyme?
b. Describe and explain the significance of the effect of acetyl coenzyme A on the Pyruvate Carboxylase enzyme.

2. a. Why would it be disadvantageous to the organism to have Glycolysis and Gluconeogenesis operating simultaneously within a cell? Briefly describe one example of reciprocal regulation of Glycolysis and Gluconeogenesis, involving an allosteric regulator. For the example chosen, write out the reaction catalyzed by the enzyme in each pathway, and indicate the nature of the effect of the regulator (e.g., inhibition or activation). 
     b. Diagram the Cori Cycle and summarize the energetic cost of this cycle in terms of "high energy" bonds of ATP. What might be the value to the organism of having the capability for such an inefficient cycle?

Copyright 1998-2007 by Joyce J. Diwan. All rights reserved.

Lecture notes on
Gluconeogenesis

Interactive Quiz     
on Gluconeogenesis  

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