Molecular Biochemistry II

Eicosanoid Synthesis

Reading:

Textbook Reading: Voet & Voet, Biochemistry, 3rd Edition, p. 959-969.

Some recent articles (optional reading): 
R. M. Garavito & A. M. Mulichak (2003) "The structure of mammalian cyclooxygenases,"  Annu. Rev. Biophys. Biomol. Struct. 32: 183-206.
R. J. Soberman & P. Christmas (2003) "The organization and consequences of eicosanoid signaling," J. Clin. Invest. 111: 1107-1113.
J. M. Schwab, H. J. Schluesener, R. Meyermann & C. N. Serhan (2003) "COX-3 the enzyme and the concept: steps towards highly specialized pathways and precision therapeutics?" Prostaglandins, Leukotrienes & Essential Fatty Acids 69: 339-343.
C. Brink, S.-E. Dahlen, J. Drazen, J. F. Evans, D. W. P. Hay, S. Nicosia, C. N. Serhan, T. Shimizu & T. Yokomizo (2003) "International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors," Pharmacol. Rev. 55: 195-227.
M. Romano & J. Claria (2003) "Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy," FASEB J. 17: 1986-1995.
A. A. Spector, X. Fang, G. D. Snyder & N. L. Weintraub (2004) "Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function," Progr. in Lipid Res. 43: 55-90.
C. L. Bos, D. J. Richel, T. Ritsema, M. P. Peppelenbosch & H. H. Versteeg (2004) "Prostanoids and prostanoid receptors in signal transduction," Internat. J. Biochem. & Cell Biol. 36: 1187-1205.
A. N. Hata & R. M. Breyer (2004) "Pharmacology and signaling of prostaglandin receptors: Multiple roles in inflammation and immune modulation," Pharm. & Therapeutics 103: 147-166.
N. Ueno, Y. Takegoshi, D. Kamei, I. Kudo & M. Murakami (2005) "Coupling between cyclooxygenases and terminal prostanoid synthases," Biochem. Biophys. Res. Comm. 338: 70-76.
H. Kuhn, J. Saam, S. Eibach, H.-G. Holzhutter, I. Ivanov & M. Walther (2005) "Structural biology of mammalian lipoxygenases: Enzymatic consequences of targeted alterations of the protein structure," Biochem. Biophys. Res. Comm. 338: 93-101.
T. Okuno, T. Yokomizo, T. Hori, M. Miyano & T. Shimizu (2005) "Leukotriene B₄ receptor and the function of its helix 8," J. Biol. Chem. 280: 32049-32052.
S. Yedgar, Y. Cohen & D. Shoseyov (2006) "Control of phospholipase A₂ activities for the treatment of inflammatory conditions," Biochim. Biophys. Acta 1761: 1373-1382.
M. Luo, N. Flamand & T. G. Brock (2006) "Metabolism of arachidonic acid to eicosanoids within the nucleus," Biochim. Biophys. Acta 1761: 618-625.
O. Rådmark & B. Samuelsson (2007) "5-Lipoxygenase: Regulation and possible involvement in atherosclerosis," Prostaglandins & other Lipid Mediators 83: 162-174.
T. Klein, P. Shephard, H. Kleinert & M. Kömhoff (2007) "Regulation of cyclooxygenase-2 expression by cyclic AMP," Biochim. Biophys. Acta 1773: 1605-1618.
M. Medhora, A. Dhanasekaran, S. K. Gruenloh, L. K. Dunn, M. Gabrilovich, J. R. Falck, D. R. Harder, E. R. Jacobs & P. F. Pratt (2007) "Emerging mechanisms for growth and protection of the vasculature by cytochrome P450-derived products of arachidonic acid and other eicosanoids," Prostaglandins & other Lipid Mediators 82: 19-29.

Potential Test Question:

1a. Diagram the two reactions catalyzed by PGH₂ Synthase, giving structures of substrate and product and the name of the enzyme activity for each reaction. Name the prosthetic group and the amino acid residue that function in catalysis. What is the significance of the final product, PGH₂? 
b. Describe the mechanisms by which aspirin and ibuprofen inhibit PGH₂ Synthase.
c. Briefly describe and explain the advantages to health of taking a daily aspirin. Why are some effects of a low-dose aspirin long-lived? 

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Lecture Notes on Eicosanoid Synthesis

Interactive Quiz on      Eicosanoid Synthesis