{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/23240"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/23240","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Hydroperoxide stimulation of prostaglandin endoperoxide synthase","abstract":"ETDs are only available to UIUC Users without author permission","abstract_html":"ETDs are only available to UIUC Users without author permission","abstract_has_math":false,"creators":["Pendleton, Robert Brian"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Physics","degree_department":null,"school":null,"contributors":["Lands, William E.M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T14:07:09Z","date_published":"2011-05-07T14:07:09Z","updated_at":"2026-07-22T22:25:21Z","subjects":["Biology, General","Chemistry, Biochemistry","Health Sciences, Radiology"],"languages":["eng"],"rights":["Copyright 1990 Pendleton, Robert Brian"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9026293","(UMI)AAI9026293"],"render_values":[{"text":"AAI9026293","href":null,"code":true},{"text":"(UMI)AAI9026293","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/23240","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Lands, William E.M."]},{"key":"dc:creator","label":"Author","values":["Pendleton, Robert Brian"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T14:07:09Z","10000-01-01","1990"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physics"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology, General","Chemistry, Biochemistry","Health Sciences, Radiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1990 Pendleton, Robert Brian"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9026293","(UMI)AAI9026293","http://hdl.handle.net/2142/23240"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["ETDs are only available to UIUC Users without author permission","Hydroperoxide is required to activate prostaglandin endoperoxide synthase (PES) cyclooxygenase by formation of an enzyme-radical species (derived from a PES peroxidase intermediate), and is generated by the cyclooxygenase reaction, thereby causing a positive feedback in the rate of oxygenation (hydroperoxide amplification). A kinetic model that integrates the cyclooxygenase and peroxidase activities was proposed. Numerical integration of the kinetic rate equations was found to accurately predict both the time-course of oxygen consumption, and the levels of prostaglandin G$\\sb2$ (PGG$\\sb2$) hydroperoxide, during oxygenation of arachidonic acid (20:4n-6).","15-Hydroperoxyeicosatetraenoic acid (15-HPETE), was found to be a highly effective activator of the cyclooxygenase activity using a kinetic assay based upon the ability of hydroperoxide to overcome the antagonistic effects of sodium cyanide. Phospholipid triglyceride, and cholesterol ester hydroperoxides were ineffective, but became highly effective after enzymatic hydrolysis, and therefore, PES requires an non-esterified hydroperoxide for activation. The mono-hydroperoxy positional isomers of oxidized arachidonate had decreasing effectiveness as the hydroperoxide group was located nearer to the acid terminus, and the cyclic endoperoxy-hydroperoxides PGG$\\sb2$ and PGG$\\sb3$ had only one sixth the activity of 15-HPETE. Unexpectedly, the oxygenation of 20:5n-3 was found to be more responsive to 15-HPETE activator than the oxygenation of 20:4n-6.","Using sodium cyanide or glutathione peroxidase as hydroperoxide antagonists the hydroperoxide amplification process was found to be impaired in the reaction with eicosapentaenoate (20:5n-3). The rate constant for the initial reaction between enzyme and hydroperoxide was found to be equal for both PGG$\\sb2$ and PGG$\\sb3$ and therefore the impaired reactivity of 20:5n-3 probably did not involve the steps leading to the radical-enzyme intermediate. Using OXYSIM, a computer program for numerically integrating the proposed kinetic equations and a systematic process for adjusting the kinetic constants, it was found that the impaired hydroperoxide amplification of the 20:5n-3 reaction could be accounted for by a 4.6-fold decreased rate of oxygen insertion, and a 2.2-fold increased rate of cyclooxygenase inactivation.","These data provide a greater understanding of hydroperoxide and prostaglandin metabolism, and a mechanistic rational for the therapeutic effects of dietary 20:5n-3 in certain inflammatory and thromboembolic diseases where prostaglandin overproduction is believed to be pathologic.","Made available in DSpace on 2011-05-07T14:07:09Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9026293.pdf: 6367575 bytes, checksum: 078ba53132446d583788795f44ea4930 (MD5) Previous issue date: 1990","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T15:03:08Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:30:05-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","U of I Only"]},{"key":"dc:title","label":"Title","values":["Hydroperoxide stimulation of prostaglandin endoperoxide synthase"]}]}],"canonical_facts":{"dc:contributor":["Lands, William E.M."],"dc:creator":["Pendleton, Robert Brian"],"dc:date":["2011-05-07T14:07:09Z","10000-01-01","1990"],"dc:description":["ETDs are only available to UIUC Users without author permission","Hydroperoxide is required to activate prostaglandin endoperoxide synthase (PES) cyclooxygenase by formation of an enzyme-radical species (derived from a PES peroxidase intermediate), and is generated by the cyclooxygenase reaction, thereby causing a positive feedback in the rate of oxygenation (hydroperoxide amplification). A kinetic model that integrates the cyclooxygenase and peroxidase activities was proposed. Numerical integration of the kinetic rate equations was found to accurately predict both the time-course of oxygen consumption, and the levels of prostaglandin G$\\sb2$ (PGG$\\sb2$) hydroperoxide, during oxygenation of arachidonic acid (20:4n-6).","15-Hydroperoxyeicosatetraenoic acid (15-HPETE), was found to be a highly effective activator of the cyclooxygenase activity using a kinetic assay based upon the ability of hydroperoxide to overcome the antagonistic effects of sodium cyanide. Phospholipid triglyceride, and cholesterol ester hydroperoxides were ineffective, but became highly effective after enzymatic hydrolysis, and therefore, PES requires an non-esterified hydroperoxide for activation. The mono-hydroperoxy positional isomers of oxidized arachidonate had decreasing effectiveness as the hydroperoxide group was located nearer to the acid terminus, and the cyclic endoperoxy-hydroperoxides PGG$\\sb2$ and PGG$\\sb3$ had only one sixth the activity of 15-HPETE. Unexpectedly, the oxygenation of 20:5n-3 was found to be more responsive to 15-HPETE activator than the oxygenation of 20:4n-6.","Using sodium cyanide or glutathione peroxidase as hydroperoxide antagonists the hydroperoxide amplification process was found to be impaired in the reaction with eicosapentaenoate (20:5n-3). The rate constant for the initial reaction between enzyme and hydroperoxide was found to be equal for both PGG$\\sb2$ and PGG$\\sb3$ and therefore the impaired reactivity of 20:5n-3 probably did not involve the steps leading to the radical-enzyme intermediate. Using OXYSIM, a computer program for numerically integrating the proposed kinetic equations and a systematic process for adjusting the kinetic constants, it was found that the impaired hydroperoxide amplification of the 20:5n-3 reaction could be accounted for by a 4.6-fold decreased rate of oxygen insertion, and a 2.2-fold increased rate of cyclooxygenase inactivation.","These data provide a greater understanding of hydroperoxide and prostaglandin metabolism, and a mechanistic rational for the therapeutic effects of dietary 20:5n-3 in certain inflammatory and thromboembolic diseases where prostaglandin overproduction is believed to be pathologic.","Made available in DSpace on 2011-05-07T14:07:09Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9026293.pdf: 6367575 bytes, checksum: 078ba53132446d583788795f44ea4930 (MD5) Previous issue date: 1990","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T15:03:08Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:30:05-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","U of I Only"],"dc:identifier":["AAI9026293","(UMI)AAI9026293","http://hdl.handle.net/2142/23240"],"dc:language":["eng"],"dc:rights":["Copyright 1990 Pendleton, Robert Brian"],"dc:subject":["Biology, General","Chemistry, Biochemistry","Health Sciences, Radiology"],"dc:title":["Hydroperoxide stimulation of prostaglandin endoperoxide synthase"],"dc:type":["text"],"thesis:degree_discipline":["Physics"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:21Z"}