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The enzymology of the human prostanoid pathway

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Abstract

Prostanoids are short-lived autocrine and paracrine signaling molecules involved in a wide range of biological functions. They have been shown to be intimately involved in many different disease states when their regulation becomes dysfunctional. In order to fully understand the progression of any disease state or the biological functions of the well state, a complete evaluation of the genomics, proteomics, and metabolomics of the system is necessary. This review is focused on the enzymology for the enzymes involved in the synthesis of the prostanoids (prostaglandins, prostacyclins and thromboxanes). In particular, the isolation and purification of the enzymes, their enzymatic parameters and catalytic mechanisms are presented.

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References

  1. Watanabe K (2011) Recent reports about enzymes related to the synthesis of prostaglandin (PG) F2 (PGF2α and 9α, 11β-PGF2). J Biochem 150:593–596. https://doi.org/10.1093/jb/mvr116

    Article  CAS  PubMed  Google Scholar 

  2. Cao H, Yu R, Tao Y, Nikolic D, van Breemen RB (2011) Measurement of cyclooxygenase inhibition using liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal 54:230–235. https://doi.org/10.1016/j.jpba.2010.08.001

    Article  CAS  PubMed  Google Scholar 

  3. Cuendet M, Mesecar AD, DeWitt DL, Pezzuto JM (2006) An ELISA method to measure inhibition of the COX enzymes. Nat Protoc 1:1915–1921. https://doi.org/10.1038/nprot.2006.308

    Article  CAS  PubMed  Google Scholar 

  4. Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide H synthases (Cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160. https://doi.org/10.1074/jbc.271.52.33157

    Article  CAS  PubMed  Google Scholar 

  5. Nemeth JF, Hochgesang GP Jr, Marnett LJ, Caprioli RM (2001) Characterization of the glycosylation sites in cyclooxygenase-2 using mass spectrometry. Biochemistry 40:3109–3116. https://doi.org/10.1021/bi002313c

    Article  CAS  PubMed  Google Scholar 

  6. Walker MC, Gierse JK (2010) In vitro assays for cyclooxygenase activity and inhibitor characterization. Methods Mol Biol 644:131–144. https://doi.org/10.1007/978-1-59745-364-6_11

    Article  CAS  PubMed  Google Scholar 

  7. Wu G, Lü J-M, van der Donk WA, Kulmacz RJ, Tsai AL (2011) Cyclooxygenase reaction mechanism of prostaglandin H synthase from deuterium kinetic isotope effects. J Inorg Biochem 105:264–272. https://doi.org/10.1016/j.jinorgbio.2010.11.015

    Article  CAS  PubMed Central  Google Scholar 

  8. Wu G, Wei C, Kulmacz RJ, Osawa Y, Tsai AL (1999) A mechanistic study of self-inactivation of the peroxidase activity in prostaglandin H synthase-1. J Biol Chem 274:9231–9237. https://doi.org/10.1074/jbc.274.14.9231

    Article  CAS  PubMed  Google Scholar 

  9. Tsai A-L, Kulmacz RJ (2010) Prostaglandin H synthase: resolved and unresolved mechanistic issues. Arch Biochem Biophys 493:103–124. https://doi.org/10.1016/j.abb.2009.08.019

    Article  CAS  PubMed  Google Scholar 

  10. Palmer M, Chan A, Dieckmann T, Honek J (2012) The cyclooxygenase reaction. Biochemical Pharmacology, 1st edn. Wiley, Hoboken, pp 205–206

    Google Scholar 

  11. Liu Y, Roth JP (2016) A revised mechanism for human cyclooxygenase-2. J Biol Chem 291:948–958. https://doi.org/10.1074/jbc.M115.668038

    Article  CAS  PubMed  Google Scholar 

  12. Laneuville O, Breuer DK, Dewitt DL, Hla T, Funk C, Smith WL (1994) Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther 271:927–934

    CAS  PubMed  Google Scholar 

  13. Barnett J, Chow J, Ives D, Chiou M, Mackenzie R, Osen E 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 209:130–139. https://doi.org/10.1016/0167-4838(94)90148-1

    Article  Google Scholar 

  14. Blobaum AL, Xu S, Rowlinson SW, Duggan KC, Banerjee S, Kudalkar SN, Birmingham WR, Ghebreselasie K, Marnett L (2015) Action at a distance: mutations of peripheral residues transform rapid reversible inhibitors to slow, tight binders of cyclooxygenase-2. J Biol Chem 290:12793–12803. https://doi.org/10.1074/jbc.M114.635987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Miyamoto T, Ogino N, Yamamoto S, Hayaishi O (1976) Purification of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. J Biol Chem 251:2629–2636

    CAS  PubMed  Google Scholar 

  16. Rogge CE, Ho B, Liu W, Kulmacz RJ, Tsai A-L (2006) Role of Tyr348 in Tyr385 radical dynamics and cyclooxygenase inhibitor interactions in Prostaglandin H Synthase-2. Biochemistry 45:523–532. https://doi.org/10.1021/bi051235w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li X, Mazaleuskaya LL, Yuan C, Ballantyne LL, Meng H, Smith WL et al (2018) Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory functions. J Lipid Res 59:89–101. https://doi.org/10.1194/jlr.M079996

    Article  CAS  PubMed  Google Scholar 

  18. Marshall PJ, Kulmacz RJ, Lands WEM (1978) Constraints on prostaglandin biosynthesis in tissues. J Biol Chem 262:3510–3517

    Google Scholar 

  19. Inui T, Mase M, Shirota R, Nagashima M, Okada T, Urade Y (2014) Lipocalin-type prostaglandin D synthase scavenges biliverdin in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage. J Cereb Blood Flow Metab 34:1558–1567. https://doi.org/10.1038/jcbfm.2014.127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Urade Y, Fujimoto N, Hayaishi O (1985) Purification and characterization of rat brain prostaglandin D synthetase. J Biol Chem 260:12410–12415

    CAS  PubMed  Google Scholar 

  21. Urade Y, Fujimoto N, Ujihara M, Hayaishi O (1987) Biochemical and immunological characterization of rat spleen prostaglandin D synthetase. J Biol Chem 262:3820–3825

    CAS  PubMed  Google Scholar 

  22. Hoffmann A, Conradt HS, Gross G, Nimtz M, Lottspeich F, Wurster U (1993) Purification and chemical characterization of beta-trace protein from human cerebrospinal fluid: its identification as prostaglandin D synthase. J Neurochem 61:451–456. https://doi.org/10.1111/j.1471-4159.1993.tb02145.x

    Article  CAS  PubMed  Google Scholar 

  23. Harrington MG, Fonteh AN, Biringer RG, Hühmer AFR, Cowan RP (2006) Prostaglandin D synthase isoforms from cerebrospinal fluid vary with brain pathology. Dis Markers 22:281–289. https://doi.org/10.1155/2006/241817

    Article  Google Scholar 

  24. Zhou Y, Shaw N, Li Y, Zhao Y, Zhang R, Liu ZJ (2010) Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules. FASEB J 24:4668–4677. https://doi.org/10.1096/fj.10-164863

    Article  CAS  PubMed  Google Scholar 

  25. Tokugawa Y, Kunishige I, Kubota Y, Shimoya K, Nobunaga T, Kimura T et al (1998) Lipocalin-type prostaglandin D synthase in human male reproductive organs and seminal plasma. Biol Reprod 58:600–607. https://doi.org/10.1095/biolreprod58.2.600

    Article  CAS  PubMed  Google Scholar 

  26. Kumasaka T, Aritake K, Ago H, Irikura D, Tsurumura T, Yamamoto M et al (2009) Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase. J Biol Chem 284:22344–22352. https://doi.org/10.1074/jbc.M109.018341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Brose SA, Thuen BT, Golovko MY (2011) LC/MS/MS method for analysis of E2 series prostaglandins and isoprostanes. J Lipid Res 52:850–859. https://doi.org/10.1194/jlr.D013441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Biringer RG, Horner J, Fonteh AN, Kauffman S, Hühmer AFR et al (2011) Absolute quantification of eicosanoid pathway proteins using a linear ion trap Mass spectrometer. Thermo Scientific application note 509; 2011. Available from: https://assets.thermofisher.com/TFS-Assets/CMD/Application-Notes/AN-63382-Absolute-Quantification-of-Eicosanoid-Pathways-Velos-Pro-Proteomics.pdf

  29. Mahmud I, Ueda N, Yamaguchi H, Yamashita R, Yamamoto S, Kanaoka Y et al (1997) Prostaglandin D synthase in human megakaryoblastic cells. J Biol Chem 272:28263–28266. https://doi.org/10.1074/jbc.272.45.28263

    Article  CAS  PubMed  Google Scholar 

  30. Urade Y, Mohri I, Aritake K, Inoue T, Miyano M (2006) Biochemical and structural characteristics of hematopoietic prostaglandin D synthase: From evolutionary analysis to drug designing. In: Morikawa D, Tate SI (eds) Functional and structural biology on the liponetwork. Transworld Research Network, Kerala, pp 135–164

    Google Scholar 

  31. Inoue T, Irikura D, Okazaki N, Kinugasa S, Matsumura H, Uodome N et al (2003) Mechanism of metal activation of human hematopoietic prostaglandin D synthase. Nat Struct Biol 10:291–296. https://doi.org/10.1038/nsb907

    Article  CAS  PubMed  Google Scholar 

  32. Kanaoka Y, Ago H, Inagaki E, Nanayama T, Miyano M, Kikun R et al (1997) Cloning and crystal structure of hematopoietic prostaglandin D synthase. Cell 90:1085–1095. https://doi.org/10.1016/s0092-8674(00)80374-8

    Article  CAS  PubMed  Google Scholar 

  33. Jowsey IR, Thomson AM, Flanagan JU, Murdock PR, Moore GB, Meyer DJ et al (2001) (2001) Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Biochem J 359:507–516. https://doi.org/10.1042/0264-6021:3590507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Takahashi S, Tsurumura T, Aritake K, Furubayashi N, Sato M, Yamanaka M et al (2010) High-quality crystals of human haematopoietic prostaglandin D synthase with novel inhibitors. Acta Crystallogr 66:846–850. https://doi.org/10.1107/S1744309110020828

    Article  CAS  Google Scholar 

  35. Pinzar E, Miyano M, Kanaoka Y, Urade Y, Hayaishi O (2000) Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis. J Biol Chem 275:31239–31244. https://doi.org/10.1074/jbc.M000750200

    Article  CAS  PubMed  Google Scholar 

  36. Jegerschöld C, Pawelzik SC, Purhonen P, Bhakat P, Gheorghe KR, Gyobu N et al (2008) Structural basis for induced formation of the inflammatory mediator prostaglandin E2. Proc Natl Acad Sci USA 105:11110–11115. https://doi.org/10.1073/pnas.0802894105

    Article  PubMed  Google Scholar 

  37. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R et al (2004) Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet 36:40–45. https://doi.org/10.1038/ng1285

    Article  Google Scholar 

  38. Thorén S, Weinander R, Saha S, Jegerschöld C, Pettersson PL, Samuelsson B et al (2003) Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination. J Biol Chem 278:22199–22209. https://doi.org/10.1074/jbc.M303227200

    Article  CAS  PubMed  Google Scholar 

  39. Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci USA 96:7220–7225. https://doi.org/10.1073/pnas.96.13.7220

    Article  CAS  PubMed  Google Scholar 

  40. Koeberle A, Werz O (2015) Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders. Biochem Pharmacol 98:1–15. https://doi.org/10.1016/j.bcp.2015.06.022

    Article  CAS  PubMed  Google Scholar 

  41. Hamza A, Tong M, AbdulHameed MD, Liu J, Goren AC, Tai HH et al (2010) Understanding microscopic binding of human microsomal prostaglandin E synthase-1 (mPGES-1) trimer with substrate PGH2 and cofactor GSH: insights from computational alanine scanning and site-directed mutagenesis. J Phys Chem B 114:5605–5616. https://doi.org/10.1021/jp100668y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Pettersson PL, Thorén S (2005) Jakobsson PJ (2005) Human microsomal prostaglandin E synthase 1: a member of the MAPEG protein superfamily. Methods Enzymol 401:147–161. https://doi.org/10.1016/S0076-6879(05)01009-8

    Article  CAS  PubMed  Google Scholar 

  43. Yamada T, Komoto J, Watanabe K, Ohmiya Y, Takusagawa F (2005) Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2)”. J Mol Biol 348:1163–1176. https://doi.org/10.1016/j.jmb.2005.03.035

    Article  CAS  PubMed  Google Scholar 

  44. Murakami M, Nakashima K, Kamei D, Masuda S, Ishikawa Y, Ishii T et al (2003) Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2. J Biol Chem 278:37937–37947. https://doi.org/10.1074/jbc.M305108200

    Article  CAS  PubMed  Google Scholar 

  45. Watanabe K, Kurihara K (1999) Suzuki T (1999) Purification and characterization of membrane-bound prostaglandin E synthase from bovine heart. Biochim Biophys Acta 1439:406–414. https://doi.org/10.1016/s1388-1981(99)00084-0

    Article  CAS  PubMed  Google Scholar 

  46. Takusagawa F (2013) Microsomal prostaglandin E synthase type 2 (mPGES2) is a glutathione-dependent heme protein, and dithiothreitol dissociates the bound heme to produce active prostaglandin E2 synthase in vitro. J Biol Chem 288:10166–10175. https://doi.org/10.1074/jbc.M112.418475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tanikawa N, Ohmiya Y, Ohkubo H, Hashimoto K, Kangawa K, Kojima M et al (2002) Identification and characterization of a novel type of membrane-associated prostaglandin E synthase. Biochem Biophys Res Commun 291:884–889. https://doi.org/10.1006/bbrc.2002.6531

    Article  CAS  PubMed  Google Scholar 

  48. Watanabe K, Ohkubo H, Niwa H, Tanikawa N, Koda N, Ito S et al (2003) Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2. Biochem Biophys Res Commun 306:577–581. https://doi.org/10.1016/s0006-291x(03)01025-8

    Article  CAS  PubMed  Google Scholar 

  49. Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE (2001) Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem 276:15571–15574. https://doi.org/10.1074/jbc.C100055200

    Article  CAS  PubMed  Google Scholar 

  50. Murakami M, Naraba H, Tanioka T, Semmyo N, Nakatani Y, Kojima F et al (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275:32783–32792. https://doi.org/10.1074/jbc.M003505200

    Article  CAS  PubMed  Google Scholar 

  51. Tanioka T, Nakatani Y, Semmyo N, Murakami M, Kudo I (2000) Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 275:32775–32782. https://doi.org/10.1074/jbc.M003504200

    Article  CAS  PubMed  Google Scholar 

  52. Urbanet R, Nguyen Dinh Cat A, Feraco A, Venteclef N, El Mogrhabi S, Sierra-Ramos C et al (2015) Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of prostaglandin D2 synthase. Hypertension 66:149–157. https://doi.org/10.1161/HYPERTENSIONAHA.114.04981

    Article  CAS  PubMed  Google Scholar 

  53. Lin Y, Wu KK, Ruan KH (1998) Characterization of the secondary structure and membrane interaction of the putative membrane anchor domains of prostaglandin I2 synthase and cytochrome P450 2C1. Arch Biochem Biophys 352:78–84. https://doi.org/10.1006/abbi.1998.0599

    Article  CAS  PubMed  Google Scholar 

  54. Shyue SK, Ruan KH, Wang LH, Wu KK (1997) Prostacyclin synthase active sites. Identification by molecular modeling-guided site-directed mutagenesis. J Biol Chem 272:3657–3662. https://doi.org/10.1074/jbc.272.6.3657

    Article  CAS  PubMed  Google Scholar 

  55. Hatae T, Hara S, Yokoyama C, Yabuk T, Inoue H, Ullrich V et al (1996) Site-directed mutagenesis of human prostacyclin synthase: Alteration of Cys 441 of the Cys-pocket, and Glu 347 and Arg 35° of the EXXR motif. FEBS Lett 389:268–272. https://doi.org/10.1016/0014-5793(96)00600-x

    Article  CAS  PubMed  Google Scholar 

  56. DeWitt DL, Smith WL (1995) Purification of prostacyclin synthase from bovine aorta by immunoaffinity chromatography. Evidence that the enzyme is a hemoprotein. J Biol Chem 258:3285–3293

    Google Scholar 

  57. Wade ML, Voelkel NF, Fitzpatrick FA (1995) Suicide Inactivation of Prostaglandin I2 Synthase: Characterization of Mechanism-Based Inactivation with Isolated Enzyme and Endothelial Cells. Arch Biochem Biophys 321:453–458. https://doi.org/10.1006/abbi.1995.1417

    Article  CAS  PubMed  Google Scholar 

  58. Hecker M, Ullrich V (1989) On the mechanism of prostacyclin and thromboxane A2 biosynthesis. J Biol Chem 264:141–150

    CAS  PubMed  Google Scholar 

  59. Yeh HC, Gerfen GJ, Wang JS, Tsai AL, Wang LH (2009) Characterization of the peroxidase mechanism upon reaction of prostacyclin synthase with peracetic acid. Identification of a tyrosyl radical intermediate. Biochemistry 48:917–928. https://doi.org/10.1021/bi801382v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Watanabe K, Woodward DF (2015) The endocannabinoidome: the world of endocannabinoids and related mediators. In: Piscitelli F (ed) Di Marzo V. Elsevier, New York, pp 101–110

    Google Scholar 

  61. Suzuki-Yamamoto T, Toida K, Sugimoto Y, Ishimura K (2009) Colocalization of prostaglandin F2 receptor FP and prostaglandin F synthase-I in the spinal cord. J Lipid Res 50:1996–2003. https://doi.org/10.1194/jlr.M800543-JLR200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Guo C, Wang W, Liu C, Myatt L, Sun K (2014) Induction of PGF2α Induction of PGF2α synthesis by cortisol through GR dependent induction of CBR1 in human amnion fibroblasts. Endocrinology 155:3017–3024. https://doi.org/10.1210/en.2013-1848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Silvestri C, Martella A, Poloso NJ, Piscitelli F, Capasso R, Izzo A et al (2013) Anandamide-derived prostamide F2α negatively regulates adipogenesis. J Biol Chem 288:23307–23321. https://doi.org/10.1074/jbc.M113.489906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Watanabe K, Yoshida R, Shimizu T, Hayaishi O (1985) Enzymatic formation of prostaglandin F2 alpha from prostaglandin H2 and D2. Purification and properties of prostaglandin F synthetase from bovine lung. J Biol Chem 260:7035–7041

    CAS  PubMed  Google Scholar 

  65. Matsunaga T, Shintani S, Hara A (2006) Multiplicity of mammalian reductases for xenobiotic carbonyl compounds. Drug Metab Pharmacokinet 21:1–18. https://doi.org/10.2133/dmpk.21.1

    Article  CAS  PubMed  Google Scholar 

  66. Moriuchi H, Koda N, Okuda-Ashitaka E, Daiyasu H, Ogasawara K, Toh H et al (2008) Molecular characterization of a novel type of prostamide/prostaglandin F synthase, belonging to the thioredoxin-like superfamily. J Biol Chem 283:792–801. https://doi.org/10.1074/jbc.M705638200

    Article  CAS  PubMed  Google Scholar 

  67. Zhou X, Li D, Resnick MB, Wands J, Cao W (2013) NADPH oxidase NOX5-S and nuclear factor κB1 mediate acid-induced microsomal prostaglandin E synthase-1 expression in Barrett's esophageal adenocarcinoma cells. Mol Pharmacol 83:978–990. https://doi.org/10.1124/mol.112.083287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Grippo JF, Holmgren A, Pratt WB (1985) Proof that the endogenous, heat-stable glucocorticoid receptor-activating factor is thioredoxin. J Biol Chem 260:93–97

    CAS  PubMed  Google Scholar 

  69. Arnér ES, Holmgren A (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 26:6102–6109. https://doi.org/10.1046/j.1432-1327.2000.01701.x

    Article  Google Scholar 

  70. Bateman RL, Rauh D, Tavshanjian B, Shokat KM (2008) Human carbonyl reductase 1 is an S-nitrosoglutathione reductase. J Biol Chem 283:35756–35762. https://doi.org/10.1074/jbc.M807125200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kassner N, Huse K, Martin HJ, Gödtel-Armbrust U, Metzge A, Meineke I et al (2008) Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos 36:2113–2120. https://doi.org/10.1124/dmd.108.022251

    Article  CAS  PubMed  Google Scholar 

  72. Gonzalez-Covarrubias V, Ghosh D, Lakhman SS, Pendyala L, Blanco JG (2007) A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity. Drug Metab Dispos 35:973–980. https://doi.org/10.1124/dmd.107.014779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wermuth B (1981) Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. J Biol Chem 256:1206–1213

    CAS  PubMed  Google Scholar 

  74. Fujimoto K, Hara M, Yamada H, Sakurai M, Inaba A, Tomomura A et al (2001) Role of the conserved Ser–Tyr–Lys triad of the SDR family in sepiapterin reductase. Chem Biol Interact 130–132:825–832. https://doi.org/10.1016/s0009-2797(00)00238-6

    Article  PubMed  Google Scholar 

  75. Gani OA, Adekoya OA, Giurato L, Spyrakis F, Cozzini P, Guccione S et al (2008) Theoretical calculations of the catalytic triad in short-chain alcohol dehydrogenases/reductases. Biophys J 94:1412–1427. https://doi.org/10.1529/biophysj.107.111096

    Article  CAS  PubMed  Google Scholar 

  76. Liu SQ, Bhatnagar A, Ansari NH, Srivastava SK (1993) Identification of the reactive cysteine residue in human placenta aldose reductase. Biochim Biophys Acta 1164:268–272. https://doi.org/10.1016/0167-4838(93)90258-s

    Article  CAS  PubMed  Google Scholar 

  77. Niesen FH, Schultz L, Jadhav A, Bhatia C, Guo K, Maloney DJ et al (2010) High-affinity inhibitors of human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase: mechanisms of inhibition and structure-activity relationships. PLoS ONE 5:e13719. https://doi.org/10.1371/journal.pone.0013719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kabututu Z, Manin M, Pointud JC, Maruyama T, Nagata N, Lambert S et al (2009) Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7. J Biochem 145:161–168. https://doi.org/10.1093/jb/mvn152

    Article  CAS  PubMed  Google Scholar 

  79. Nagata N, Kusakari Y, Fukunishi Y, Inoue T, Urade Y (2011) Catalytic mechanism of the primary human prostaglandinF2a synthase, aldo-keto reductase 1B1 – prostaglandin D2 synthase activity in the absence of NADP(H). FEBS J 278:1288–1298. https://doi.org/10.1111/j.1742-4658.2011.08049.x

    Article  CAS  PubMed  Google Scholar 

  80. Jaquinod M, Potier N, Klarskov K, Reymann JM, Sorokine O, Kieffer S et al (1993) Sequence of pig lens aldose reductase and electrospray mass spectrometry of non-covalent and covalent complexes. Eur J Biochem 218:893–903. https://doi.org/10.1111/j.1432-1033.1993.tb18445.x

    Article  CAS  PubMed  Google Scholar 

  81. Khanna M, Qin KN, Wang RW, Cheng KC (1995) Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases. J Biol Chem 270:20162–20168. https://doi.org/10.1074/jbc.270.34.20162

    Article  CAS  PubMed  Google Scholar 

  82. O'Connor T, Ireland LS, Harrison DJ, Hayes JD (1999) Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. Biochem J 343:487–504

    Article  CAS  Google Scholar 

  83. Suzuki-Yamamoto T, Nishizawa M, Fukui M, Okuda-Ashitaka E, Nakajima T, Ito S et al (1999) cDNA cloning, expression and characterization of human prostaglandin F synthase. FEBS Lett 462:335–340. https://doi.org/10.1016/s0014-5793(99)01551-3

    Article  CAS  PubMed  Google Scholar 

  84. Penning TM, Burczynski ME, Jez JM, Lin HK, Ma H et al (2001) Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3). Mol Cell Endocrinol 171:137–149. https://doi.org/10.1016/s0303-7207(00)00426-3

    Article  CAS  PubMed  Google Scholar 

  85. Komoto J, Yamada T, Watanabe K, Takusagawa F (2004) Crystal structure of human prostaglandin F synthase (AKR1C3). Biochemistry 43:2188–2198. https://doi.org/10.1021/bi036046x

    Article  CAS  PubMed  Google Scholar 

  86. Lovering AL, Ride JP, Bunce CM, Desmond JC, Cummings SM, White SA (2004) Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin. Cancer Res 64:1802–1810. https://doi.org/10.1158/0008-5472.can-03-2847

    Article  CAS  PubMed  Google Scholar 

  87. Ricciotti E, FitzGerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31:986–1000. https://doi.org/10.1161/ATVBAHA.110.207449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Smith WL, Urade Y, Jakobsson PJ (2011) Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis. Chem Rev 111:5821–5865. https://doi.org/10.1021/cr2002992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Wolfe LS, Rostworowski K, Marion J (1976) Endogenous formation of the prostaglandin endoperoxine metabolite, thromboxane B2, by brain tissue. Biochem Biophys Res Commun 70:907–913. https://doi.org/10.1016/0006-291x(76)90677-x

    Article  CAS  PubMed  Google Scholar 

  90. Ohashi K, Ruan KH, Kulmacz RJ, Wu KK, Wang LH (1992) Primary structure of human thromboxane synthase determined from the cDNA sequence. J Biol Chem 267:789–793

    CAS  PubMed  Google Scholar 

  91. Chevalier D, Lo-Guidice JM, Sergent E, Allorge D, Debuysère H, Ferrari N et al (2001) Identification of genetic variants in the human thromboxane synthase gene (CYP5A1). Mutat Res 432:61–67. https://doi.org/10.1016/s1383-5726(00)00004-2

    Article  CAS  PubMed  Google Scholar 

  92. Geneviève D, Proulle V, Isidor B, Bellais S, Serre V, Djouadi F et al (2008) Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome). Nat Genet 40:284–286. https://doi.org/10.1038/ng.2007.66

    Article  CAS  PubMed  Google Scholar 

  93. Chen CY, Poole EM, Ulrich CM, Kulmacz RJ, Wang LH (2012) Functional analysis of human thromboxane synthase polymorphic variants. Pharmacogenet Genomics 22:653–658. https://doi.org/10.1097/FPC.0b013e3283562d82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wang LH, Matijevic-Aleksic N, Hsu PY, Ruan KH, Wu KK, Kulmacz RJ (1996) Identification of thromboxane A2 synthase active site residues by molecular modeling-guided site-directed mutagenesis. J Biol Chem 271:19970–19975. https://doi.org/10.1074/jbc.271.33.19970

    Article  CAS  PubMed  Google Scholar 

  95. Shen RF, Tai HH (1986) Immunoaffinity purification and characterization of thromboxane synthase from porcine lung. J Biol Chem 261:11592–11599

    CAS  PubMed  Google Scholar 

  96. Hall ER, Tuan WM, Venton DL (1986) Production of platelet thromboxane A2 inactivates purified human platelet thromboxane synthase. Biochem J 233:637–641. https://doi.org/10.1042/bj2330637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hsu PY, Tsai AL, Wan LH (2000) Identification of thromboxane synthase amino acid residues involved in heme-propionate binding. Arch Biochem Biophys 383:119–127. https://doi.org/10.1006/abbi.2000.2041

    Article  CAS  PubMed  Google Scholar 

  98. Hall ER, Townsend GL, Linthicum DS, Frasier-Scott KF (1991) Substrate inactivation of lung thromboxane synthase preferentially decreases thromboxane A2 production. Prostaglandins Leukot Essent Fatty Acids 42:31–37. https://doi.org/10.1016/0952-3278(91)90063-b

    Article  CAS  PubMed  Google Scholar 

  99. Jones DA, Fitzpatrick FA (1991) Thromboxane A2 synthase modification during “suicide” inactivation. J Biol Chem 266:23510–23514

    CAS  PubMed  Google Scholar 

  100. Biringer RG (2019) The role of eicosanoids in Alzheimer's disease. Int J Environ Res Public Health. https://doi.org/10.3390/ijerph16142560

    Article  PubMed  PubMed Central  Google Scholar 

  101. Shibata T, Kondo M, Osawa T, Shibata N, Kobayashi M, Uchida K (2002) 15-deoxy-delta 12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes. J Biol Chem. 277(12):10459–10466. https://doi.org/10.1074/jbc.M110314200

    Article  CAS  PubMed  Google Scholar 

  102. Liston TE, Roberts LJ 2nd (1985) Metabolic fate of radiolabeled prostaglandin D2 in a normal human male volunteer. J Biol Chem 260(24):13172–13180

    CAS  PubMed  Google Scholar 

  103. Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ 2nd (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 87:9383–9387. https://doi.org/10.1073/pnas.87.23.9383

    Article  CAS  PubMed  Google Scholar 

  104. Campbell WB, Holland OB, Adams BV, Gomez-Sanchez CE (1985) Urinary excretion of prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2 in normotensive and hypertensive subjects on varying sodium intakes. Hypertension 4:735–741. https://doi.org/10.1161/01.hyp.4.5.735

    Article  Google Scholar 

  105. Frölich JC, Wilson TW, Sweetman BJ, Smigel M, Nies AS, Carr K et al (1975 Apr) (1975) Urinary prostaglandins. Identif Orig J Clin Invest 55(4):763–770. https://doi.org/10.1172/JCI107987

    Article  Google Scholar 

  106. Morrow JD, Chen Y, Brame CJ, Yang J, Sanchez SC, Xu J, Zackert WE, Awad JA, Roberts LJ (1999) The isoprostanes: unique prostaglandin-like products of free-radical-initiated lipid peroxidation. Drug Metab Rev 31:117–139. https://doi.org/10.1081/dmr-100101910

    Article  CAS  PubMed  Google Scholar 

  107. Jadoon S, Malik A (2018) A comprehensive review article on isoprostanes as biological markers. Biochem Pharmacol (Los Angel) 7:2. https://doi.org/10.4172/2167-0501.1000246

    Article  Google Scholar 

  108. Benndorf RA, Schwedhelm E, Gnann A, Taheri R, Kom G, Didié M et al (2008) Isoprostanes inhibit vascular endothelial growth factor-induced endothelial cell migration, tube formation, and cardiac vessel sprouting in vitro, as well as angiogenesis in vivo via activation of the thromboxane A(2) receptor: a potential link between oxidative stress and impaired angiogenesis. Circ Res 103:1037–1046. https://doi.org/10.1161/CIRCRESAHA.108.184036

    Article  CAS  PubMed  Google Scholar 

  109. Diczfalusy U, Alexson SE (1990) Identification of metabolites from peroxisomal beta-oxidation of prostaglandins. J Lipid Res 31:307–314

    CAS  PubMed  Google Scholar 

  110. Brunoldi EM, Zanoni G, Vidari G, Sasi S, Freeman ML, Milne GL, Morrow JD (2007) Cyclopentenone prostaglandin, 15-deoxy-Delta 12,14-PGJ2, is metabolized by HepG2 cells via conjugation with glutathione. Chem Res Toxicol 20:1528–1535. https://doi.org/10.1021/tx700231a

    Article  CAS  PubMed  Google Scholar 

  111. Stanley D, Kim Y (2011) Prostaglandins and their receptors in insect biology. Front Endocrinol (Lausanne) 2:105. https://doi.org/10.3389/fendo.2011.00105

    Article  Google Scholar 

  112. Di Costanzo F, Di Dato V, Ianora A, Romano G (2019) Prostaglandins in marine organisms: a review. Mar Drugs. https://doi.org/10.3390/md17070428

    Article  PubMed  PubMed Central  Google Scholar 

  113. Groenewald EG, van der Westhuizen AJ (1997) Prostaglandins and related substances in plants. Bot Rev 63:199–220. https://doi.org/10.1007/BF02857948

    Article  Google Scholar 

  114. Rand AA, Barnych B, Morisseau C, Cajka T, Lee KSS, Panigrahy D, Hammock BD (2017) Cyclooxygenase-derived proangiogenic metabolites of epoxyeicosatrienoic acids. Proc Natl Acad Sci USA 114:4370–4375. https://doi.org/10.1073/pnas.1616893114

    Article  CAS  PubMed  Google Scholar 

  115. Blobaum AL, Xu S, Rowlinson SW, Duggan KC, Banerjee S, Kudalkar SN et al (2015) Action at a distance: mutations of peripheral residues transform rapid reversible inhibitors to slow, tight binders of cyclooxygenase-2. J Biol Chem 290:12793–12803. https://doi.org/10.1074/jbc.M114.635987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Fukuhara A, Yamada M, Fujimori K, Miyamoto Y, Kusumoto T, Nakajima H et al (2012) Lipocalin-type prostaglandin D synthase protects against oxidative stress-induced neuronal cell death. Biochem J 443:75–84. https://doi.org/10.1042/BJ20111889

    Article  CAS  PubMed  Google Scholar 

  117. Watanabe K, Kurihara K, Tokunaga Y, Hayaishi O (1997) Two types of microsomal prostaglandin E synthase: glutathione-dependent and -independent prostaglandin E synthases. Biochem Biophys Res Commun 235:148–152. https://doi.org/10.1006/bbrc.1997.6708

    Article  CAS  PubMed  Google Scholar 

  118. Li YC, Chiang CW, Yeh HC, Hsu PY, Whitby FG, Wang LH et al (2007) Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligand-specific heme conformation change. J Biol Chem 283:2917–2926. https://doi.org/10.1074/jbc.M707470200

    Article  CAS  PubMed  Google Scholar 

  119. Wada M, Yokoyama C, Hatae T, Shimonishi M, Nakamura M, Imai Y et al (2004) Purification and characterization of recombinant human prostacyclin synthase. J Biochem 135:455–463. https://doi.org/10.1093/jb/mvh059

    Article  CAS  PubMed  Google Scholar 

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Biringer, R.G. The enzymology of the human prostanoid pathway. Mol Biol Rep 47, 4569–4586 (2020). https://doi.org/10.1007/s11033-020-05526-z

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