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CYCLOOXYGENASE

Presentasi Enzimologi. CYCLOOXYGENASE. Sofi Siti Shofiyah (20510038). Agenda Presentasi. Pendahuluan. Cyclooxygenase (COX). Kelas Enzim Cyclooxygenase. Nama lain: Prostaglandin H2 Synthase (PGHS), Prostaglandin endoperoxide synthases (PES). EC. 1. 14. 99. 1.

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CYCLOOXYGENASE

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  1. PresentasiEnzimologi CYCLOOXYGENASE SofiSitiShofiyah (20510038)

  2. Agenda Presentasi Presentasi Enzimologi: Cyclooxygenase

  3. Pendahuluan Presentasi Enzimologi: Cyclooxygenase

  4. Cyclooxygenase (COX) Presentasi Enzimologi: Cyclooxygenase

  5. KelasEnzimCyclooxygenase • Nama lain: Prostaglandin H2 Synthase (PGHS), Prostaglandin endoperoxidesynthases (PES) EC. 1. 14. 99. 1 Presentasi Enzimologi: Cyclooxygenase

  6. JenisEnzimCyclooxygenase • JenisCylcooxygenase: Presentasi Enzimologi: Cyclooxygenase

  7. IsolasidanPemurnian Presentasi Enzimologi: Cyclooxygenase

  8. MetodeIsolasidanPemurnian Sheep vesicular glands Isolasi Supernatan 54 % (NH4)2SO4 DEAE Cellulose Pemurnian Flurbiprofen-Sepharose Isoelectric Focusing Sephadex G-200 Enzim PresentasiEnzimologi: Cyclooxygenase

  9. UjiKarakteristikEnzim Presentasi Enzimologi: Cyclooxygenase

  10. SDS Page 1 2 3 4 Keterangan : 1 : 54% (NH4)2SO4 2: DEAE -cellulose 3: Flurbiprofen-Sepharose 4: isoelectric focusing-Sephadex G-200 Presentasi Enzimologi: Cyclooxygenase

  11. Strukturcyclooxygenase Presentasi Enzimologi: Cyclooxygenase

  12. StrukturCyclooxygease • Stuktur COX1  1994 oleh Daniel Picot • 576 asam amino • Beratmolekul 70kDa • Sturktur COX2 1996 oleh Ravi G Kurumbail • 607 asam amino • Beratmolekul 72 kDa Presentasi Enzimologi: Cyclooxygenase

  13. StrukturDimer COX 1 Presentasi Enzimologi: Cyclooxygenase

  14. Struktur COX1 Presentasi Enzimologi: Cyclooxygenase

  15. Catalytic Domain Presentasi Enzimologi: Cyclooxygenase

  16. SisiAktifPeroksidase Presentasi Enzimologi: Cyclooxygenase

  17. SisiAkifCyclooxygenase Presentasi Enzimologi: Cyclooxygenase

  18. PerbedaanStuktur COX -1 dan COX-2 • Signal peptide COX-1 lebihpanjang 7 residu • Memilikicelahkatalitikcyclooxygenase yang lebihlebardibandingkandengan COX-1 Presentasi Enzimologi: Cyclooxygenase

  19. Mekanismereaksi Presentasi Enzimologi: Cyclooxygenase

  20. MekanismeReaksiPeroksidase Presentasi Enzimologi: Cyclooxygenase

  21. The ‘‘branched-chain” reaction Presentasi Enzimologi: Cyclooxygenase

  22. MekanismeRadikalBebas Presentasi Enzimologi: Cyclooxygenase

  23. Regulasidaninhibisi Presentasi Enzimologi: Cyclooxygenase

  24. SistemRegulasididalamtubuh • Tanskripsi COX-2 diinduksidengancepatsebagairespondariberlebihnyadarah (plethora) pada organ • Kestabilan mRNA COX-2 and efisiensitranslasidiaturolehberbagaielemenpengatur • microRNAsdan RNA-binding proteins yang spesifikmempengaruhikestabilan m-RNA COX-2 • Regulasi COX-2 lainnyaadalahalternatifpolyadenilasi. Presentasi Enzimologi: Cyclooxygenase

  25. InhibisipadaEnzim COX Presentasi Enzimologi: Cyclooxygenase

  26. Klasifikasi Inhibitor pada COX • Irreversible inhibition contoh: Aspirin • Reversible inhibition contoh: ibuprofen • Slow, Time-dependent inhibition contoh: flurbiprofen • Selectively inhibition COX2 contoh: SC-558 Presentasi Enzimologi: Cyclooxygenase

  27. COX 1 dan COX 2 saatmengikatSC-558 Presentasi Enzimologi: Cyclooxygenase

  28. Kesimpulan • COX adalahbifungsionalenzim • Memilikiduasisiaktif, yaitusisiaktifcyclooxygenasedansisiaktifperoxidase. • Mekanismereaksiterjadidisebut branched chain radikal mechanism • Regulasi COX-2 terjadiditingkattranskripsidan post-transkripsi. • Inhibisienzimdilakukanolehsenyawa -senyawa NSAIDs Presentasi Enzimologi: Cyclooxygenase

  29. DaftarPustaka • Kurumabail, R.G., Structural basis for selective inhibition of Cyclooxygenase -2n by anti inflammantory agent, Nature(1996) volume 384 • Picot, The X-ray cristal structure of the membran protein prostaglandin H2 synthase-1. Nature (1994)vol 347, 1994 • Ah-Lim Tsai, Prostaglandin H synthase: Resolved and unresolved mechanistic issues, Archives of Biochemistry and Biophysics, 493(2010) 103–124. • Harper, Complexity of COX-2 gene regulation, Biochem. Soc. Trans. (2008) 36, 543–545. • Hemler, Martin, Purification of The Cyclooxygenase That Forms Prostaglandins, The Journal of Biological Chemistry (1976), 5576-5579. Presentasi Enzimologi: Cyclooxygenase

  30. TERIMA KASIH Presentasi Enzimologi: Cyclooxygenase

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