Fatty-Acid Substrate Interactions with Cyclo-oxygenases

  • W. L. Smith
  • C. J. Rieke
  • E. D. Thuresson
  • A. M. Mulichak
  • R. M. Garavito
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 31)

Abstract

Prostaglandin endoperoxide H synthases 1 and -2 (PGHS-1 and -2) convert arachidonic acid and O2 (along with two reducing equivalents) to PGH2 — the committing step in the formation of prostanoids (Smith and DeWitt 1996; Smith et al. 1996). PGHS-1 is often referred to as the constitutive enzyme, whereas PGHS-2 is known as the inducible isoform. They differ from one another mainly with respect to their temporal patterns of expression. The reason for the existence of the two PGHS isozymes is still unknown. One possibility is that PGHS-2 is induced and then functions at relatively low fatty-acid substrate and hydroperoxide-activator concentrations to generate prostanoid products during early stages of cell replication or differentiation, whereas PGHS-1 forms products that are involved in “housekeeping” functions when circulating hormones act on cells acutely to cause the release of higher concentrations of arachidonate (Capdevila et al. 1995; Kulmacz and Wang 1995; Kulmacz 1998; So et al. 1998).

Keywords

Glutathione Catalysis Aspirin Prostaglandin Luminal 

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References

  1. Barnett J, Chow J, Ives D, Chiou M, Mackenzie R, Osen E, Nguyen B, Tsing S, Bach C, Freire J, et al. (1994) Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system. Biochim Biophys Acta 1209:130–139CrossRefGoogle Scholar
  2. Bhattacharyya DK, Lecomte M, Rieke CJ, Garavito RM, Smith WL (1996) Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1. J Biol Chem 271:2179–2184CrossRefGoogle Scholar
  3. Breitner JC (1996) Inflammatory processes and anti-inflammatory drugs in Alzheimer’s disease: a current appraisal. Neurobiol Aging 17:789–794CrossRefGoogle Scholar
  4. Capdevila JH, Morrow JD, Belosludtsev YY, Beauchamp DR, DuBois RN, Falck JR (1995) The catalytic outcomes of the constitutive and the mitogen inducible isoforms of prostaglandin H2 synthase are markedly affected by glutathione and glutathione peroxidase. Biochemistry 34:3325–3337CrossRefGoogle Scholar
  5. Dietz R, Nastainczyk W, Ruf HH (1988) Higher oxidation states of prostaglandin H synthase. Rapid electronic spectroscopy detected two spectral intermediates during the peroxidase reaction with prostaglandin G2. Eur J Biochem 171:321–328CrossRefGoogle Scholar
  6. Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA (1991) Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J 5:2304–2312Google Scholar
  7. Gierse JK, Hauser SD, Creely DP, Koboldt C, Rangwala SH, Isakson PC, Seibert K (1995) Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem J 305:479–484Google Scholar
  8. Juranek I, Suzuki H, Yamamoto S (1999) Affinities of various mammalian arachidonate lipoxygenases and cyclooxygenases for molecular oxygen as substrate. Biochim Biophys Acta 1436:509–518CrossRefGoogle Scholar
  9. Karthein R, Dietz R, Nastainczyk W, Ruf HH (1988) Higher oxidation states of prostaglandin H synthase. EPR study of a transient tyrosyl radical in the enzyme during the peroxidase reaction. Eur J Biochem 171:313–320CrossRefGoogle Scholar
  10. Kulmacz RJ (1998) Cellular regulation of prostaglandin H synthase catalysis. FEBS Lett 430:154–157CrossRefGoogle Scholar
  11. Kulmacz RJ, Wang L-H (1995) Comparison of hydroperoxide initiator requirements for the cyclooxygenase activities of prostaglandin H synthase-1 and - 2. J Biol Chem 270:24019–24023CrossRefGoogle Scholar
  12. Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildenaus D, Miyashiro JM, Penning TD, Seibert K, Isakson PC, Stallings WC (1996) Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature 384:644–648CrossRefGoogle Scholar
  13. Lambeir AM, Markey CM, Dunford HB, Marnett LJ (1985) Spectral properties of the higher oxidation states of prostaglandin H synthase. J Biol Chem 260:14894–14896Google Scholar
  14. Lands WEM, Le Tellier PR, Rome LH, Vanderhoek JY (1973) Inhibition of prostaglandin biosynthesis. Adv Biosci 9:15–28Google Scholar
  15. Lands WEM, Sauter J, Stone GW (1978) Oxygen requirement for prostaglandin biosynthesis. Prostaglandins Med 1:117–120CrossRefGoogle Scholar
  16. Laneuville O, Breuer DK, DeWitt DL, Hla T, Funk CD, Smith WL (1994) Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther 271:927–934Google Scholar
  17. Laneuville O, Breuer DK, Xu N, Huang ZH, Gage DA, Watson JT, Lagarde M, DeWitt DL, Smith WL (1995) Fatty acid substrate specificities of human prostaglandin endoperoxide H synthases-1 and -2. Formation of 12 hydroxy-(9Z, 13E/Z, 15Z)-octadecatrienoic acids from a-linolenic acid. J Biol Chem 270:19330–19336CrossRefGoogle Scholar
  18. Levy GN (1997) Prostaglandin H synthases, nonsteroidal anti-inflammatory drugs, and colon cancer. FASEB J 11:234–247Google Scholar
  19. Luong C, Miller A, Barnett J, Chow J, Ramesha C, Browner MF (1996) Flexibility of the NSAID binding site in the structure of human cyclooxygenase2. Nat Struct Biol 3:927–933CrossRefGoogle Scholar
  20. Mancini JA, Riendeau D, Falgueyret JP, Vickers PJ, O’Neill GP (1995) Arginine 120 of prostaglandin G/H synthase-1 is required for the inhibition by nonsteroidal anti-inflammatory drugs containing a carboxylic acid moiety. J Biol Chem 270:29372–29377CrossRefGoogle Scholar
  21. Marshall PJ, Kulmacz RJ (1988) Prostaglandin H synthase: distinct binding sites for cyclooxygenase and peroxidase substrates. Arch Biochem Biophys 266:162–170CrossRefGoogle Scholar
  22. Meade EA, Smith WL, DeWitt DL (1993) Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem 268:6610–6614Google Scholar
  23. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR (1993) Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cylooxygenase. Proc Natl Acad Sci U S A 90:11693–11697CrossRefGoogle Scholar
  24. Mizuno K, Yamamoto S, Lands WEM (1982) Effects of non-steroidal anti-inflammatory drugs on fatty acid cyclooxygenase and prostaglandin hydroperoxidase activities. Prostaglandins 23:743–757Google Scholar
  25. Oates JA, Fitzgerald GA, Branch RA, Jackson EK, Knapp HR, Roberts LJ (1988) Clinical implications of prostaglandin and thromboxane A2 formation. N Engl J Med 319:689–698CrossRefGoogle Scholar
  26. O’Neill GP, Mancini JA, Kargman S, Yergey J, Kwan MY, Falgueyret JP, Abramovitz M, Kennedy BP, Ouellet M, Cromlish W, et al. (1994) Overexpression of human prostaglandin G/H synthase-1 and -2 by recombinant vaccinia virus: inhibition by nonsteroidal anti-inflammatory drugs and biosynthesis of 15-hydroxyeicosatetraenoic acid. Mol Pharmaco 145:245–254Google Scholar
  27. Otto JC, Smith WL (1994) The orientation of prostaglandin endoperoxide synthases-1 and -2 in the endoplasmic reticulum. J Biol Chem 269:19868–19875Google Scholar
  28. Otto JC, Smith WL (1996) Photolabeling of prostaglandin endoperoxide H synthase-1 with 3-trifluoro-3-(m-[1251]-iodophenyl)diazirine as a probe of membrane association and the cyclooxygenase active site. J Biol Chem 271:9906–9910CrossRefGoogle Scholar
  29. Patrignani P, Panara MR, Greco A, Fusco O, Natoli C, Iacobelli S, Cipollone F, Ganci A, Creminon C, Maclouf J, et al. (1994) Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther 271:1705–1712Google Scholar
  30. Patrono C (1994) Aspirin as an antiplatelet drug. N Engl J Med 330:1287–1294CrossRefGoogle Scholar
  31. Patrono C, Ciabattoni G, Davi G (1999): L’hromboxane biosynthesis in cardiovascular diseases. Stroke 21:IV 130–IV 133Google Scholar
  32. Picot D, Loll PJ, Garavito M (1994) The X-ray crystal structure of the mem-brane protein prostaglandin H2 synthase-1. Nature 367:243–249CrossRefGoogle Scholar
  33. Rieke CJ, Mulichak AM, Garavito RM, Smith WL (1999) The role of Arg 120 of prostaglandin endoperoxide H synthase-2 in the interaction with fatty acid substrates and inhibitors. J Biol Chem 274:17109–17114CrossRefGoogle Scholar
  34. Riendeau D, Percival MD, Boyce S, Brideau C, Charleson S, Cromlish W, Ethier D, Evans J, Falgueyret JP, Ford-Hutchinson AW, Gordon R, Greig G, Gresser M, Guay J, Kargman S, Leger S, Mancini JA, O’Neill G, Ouellet M, Rodger IW, Therien M, Wang Z, Webb JK, Wong E, Chan CC, et al. (1997) Biochemical and pharmacological profile of a tetrasubstituted furanone as a hiehlv selective COX-2 inhibitor. Br J Pharmacol 121:105–117CrossRefGoogle Scholar
  35. Shimokawa T, Kulmacz RJ, DeWitt DL, Smith WL (1990) Tyrosine 385 of prostaglandin endoperoxide synthase is required for cyclooxygenase catalysis. J Biol Chem 265:20073–20076Google Scholar
  36. Smith CJ, Zhang Y, Koboldt CM, Muhammad J, Zweifel BS, Shaffer A, Talley JJ, Masferrer JL, Seibert K, Isakson PC (1998) Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci U S A 95:13313–13318CrossRefGoogle Scholar
  37. Smith WL, DeWitt DL (1996) Prostaglandin endoperoxide H synthases-1 and - 2. In: Dixon FJ (ed) Advances in immunology, vol 62. Academic, Orlando, pp 167–215CrossRefGoogle Scholar
  38. Smith WL, Marnett LJ (1994) Prostaglandin endoperoxide synthases. In: Sigel H, Sigel A (eds) Metal ions in biological systems, vol 30. Dekker, New York, pp 163–199Google Scholar
  39. Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide Hsynthases (cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160CrossRefGoogle Scholar
  40. So O-Y, Scarafia LE, Mak AY, Callan OH, Swinney DC (1998) The dynamics of prostaglandin H synthases. Studies with prostaglandin H synthase 2 Y355F unmask mechanisms of time-dependent inhibition and allosteric activation. J Biol Chem 273:5801–5807CrossRefGoogle Scholar
  41. Spencer AG, Woods JW, Arakawa T, Singer II, Smith WL (1998) Subcellular localization of prostaglandin endoperoxide H synthases-1 and -2 by immunoelectron microscopy. J Biol Chem 273:9886–9893CrossRefGoogle Scholar
  42. Stegeman R, Pawlitz J, Stevens A, Gierse J, Stallings W, Kurumbail R (2000) Mechanism of cyclooxygenase reactions: structure of arachidonic acid bound to cyclooxygenase-2. Acta Crystallogr C (in press)Google Scholar
  43. Thun MJ, Namboodiri MM, Heath CW (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325:1593–1596CrossRefGoogle Scholar
  44. Tsai A, Hsi LC, Kulmacz RJ, Palmer G, Smith WL (1994) Characterization of the tyrosyl radicals in ovine prostaglandin H synthase-1 by isotope replacement and site-directed mutagenesis. J Biol Chem 269:5085–5091Google Scholar
  45. Tsai A, Kulmacz RJ, Palmer G (1995) Spectroscopic evidence for reaction of prostaglandin H synthase-1 tyrosyl radical with arachidonic acid. J Biol Chem 270:10503–10508CrossRefGoogle Scholar
  46. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716CrossRefGoogle Scholar
  47. Willard J, Lange RA, Hillis LD (1992) The use of aspirin in ischemic heart disease. N Engl J Med 327:175–181CrossRefGoogle Scholar
  48. Xiao G, Tsai AL, Palmer G, Boyar WC, Marshall PJ, Kulmacz RJ (1997) Analysis of hydroperoxide-induced tyrosyl radicals and lipoxygenase activity in aspirin-treated human prostaglandin H synthase-2. Biochemistry 36:1836–1845CrossRefGoogle Scholar
  49. Zhang Y, Shaffer A, Portanova J, Seibert K, Isakson PC (1997) Inhibition of cyclooxygenase-2 rapidly reverses inflammatory hyperalgesia and prostaglandin E2 production. J Pharmacol Exp Ther 283:1069–1075Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • W. L. Smith
  • C. J. Rieke
  • E. D. Thuresson
  • A. M. Mulichak
  • R. M. Garavito

There are no affiliations available

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