Reading:
Textbook Reading: Voet & Voet, Biochemistry, 3rd Edition, p. 930-938, 940-942
Some recent articles
(optional reading):
S. Kersten (2001) "Mechanisms of nutritional and hormonal regulation of
lipogenesis," EMBO reports 21: 282-286.
J. G. Wallis, J. L. Watts & J. Browse (2002) "Polyunsaturated fatty acid
synthesis: What will they think of next?" Trends in Biochem. Sci. 27: 467-473.
E. Duplus & C. Forest (2002) "Is there a single mechanism for fatty acid
regulation of gene transcription?" Biochem. Pharm. 64: 893-901.
M. R. Munday (2002) "Regulation of mammalian acetyl-CoA carboxylase," Biochem.
Soc. Trans. 30: 1059-1064.
D. G. Hardie & D. A. Pan (2002) "Regulation of fatty acid synthesis and
oxidation by the AMP-activated protein kinase," Biochem. Soc. Trans. 30:
1064-1070.
S. Smith, A. Witkowski, & A. K. Joshi (2003) "Structural and functional
organization of the animal fatty acid synthase," Progr. in Lipid Res. 42:
289-317.
M. C. Barber, N. T. Price & M. T. Travers (2005) "Structure and regulation of
acetyl-CoA carboxylase genes of metazoa," Biochim. Biophys. Acta 1733: 1-28.
S. W. White, J. Zheng, Y.-M. Zhang & C. O. Rock (2005) "The structural biology
of type II fatty acid biosynthesis," Annu. Rev. Biochem. 74: 791-831.
F. J. Asturias, J. Z. Chadick, I. K. Cheung, H. Stark, A. Witkowski, A. K. Joshi
& S. Smith (2005) "Structure and molecular organization of mammalian fatty acid
synthase," Nature Struct. Molec. Biol. 12: 225-232.
T. Maier, S. Jenni & N. Ban (2006) "Architecture of mammalian fatty acid
synthase at 4.5 Å resolution," Science 311:
1258-1262.
A. Jakobsson, R. Westerberg & A. Jacobsson (2006) "Fatty acid elongases in
mammals: Their regulation and roles in metabolism," Progr. In Lipid Res. 45:
237-249.
M. J. Wolfgang & M. D. Lane (2006) "The role of hypothalamic malonyl-CoA in
energy homeostatis," J. Biol. Chem. 281: 37265-37269.
Y.-M. Zhang, S. W. White & C. O. Rock (2006) "Inhibiting bacterial fatty acid
synthesis," J. Biol. Chem. 281: 17541-17544.
1. What enzyme catalyzes the committed step of fatty acid synthesis? Write out the 2-step reaction catalyzed by this enzyme, providing names of reactants, intermediates, and products only. Summarize the ways in which this enzyme is regulated, including by allosteric effectors and by phosphorylation. Explain the value to the cell or organism of these regulatory effects. What kinases are responsible for the regulation by phosphorylation? What physical change accompanies activation of the enzyme?
2.a. Diagram the structure of active site thioester intermediates of
the mammalian Fatty Acid Synthase, following the initial transacylase reactions.
Then draw the products
of the reaction catalyzed by Condensing Enzyme (reaction 3).
b. Diagram or describe in words the subsequent reduction and dehydration steps.
c. What might be the significance of the long flexible chain
of
the phosphopantetheine group of the acyl carrier protein domain (ACP) of
Fatty Acid Synthase?
1a. How many acetyl-CoA used for initial priming of the enzyme? ________ b. How many acetyl-CoA used for synthesis of each malonate? __________ c. How many malonate used (how many reaction cycles) per synthesis of one 16-C palminate? ________ d. Total acetyl-CoA used for priming and for syntheisis of malonate, a + b(c): ________ |
| 2a. How many ~P bonds of ATP used for synthesis of each malonate?
__________ b. Total ~P bonds of ATP used for synthesis of one 16-C palmitate, 2a(1c): ________ |
| 3a. How many NADPH used per reaction cycle? __________ b. Total NADPH used per synthesis of one 16-C palmitate, 3a(1c): _________ |
| 4. Write a balanced equation for synthesis of palmitate from acetyl-CoA,
listing net inputs and outputs:
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Copyright © 1998-2007 by Joyce J. Diwan. All rights reserved.
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