Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin
Factor Xa modified by reductive methylation (greater than 92%) loses the capacity to bind heparin as determined both by gel chromatography and by sedimentation equilibrium ultracentrifugation. The kinetic properties of methylated factor Xa differ, with respect to KM and Vmax for a synthetic tripepti...
Gespeichert in:
| Veröffentlicht in: | Biochemistry (Easton) 1990-10, Vol.29 (40), p.9412-9417 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 9417 |
|---|---|
| container_issue | 40 |
| container_start_page | 9412 |
| container_title | Biochemistry (Easton) |
| container_volume | 29 |
| creator | Owen, Barbara A Owen, Whyte G |
| description | Factor Xa modified by reductive methylation (greater than 92%) loses the capacity to bind heparin as determined both by gel chromatography and by sedimentation equilibrium ultracentrifugation. The kinetic properties of methylated factor Xa differ, with respect to KM and Vmax for a synthetic tripeptide substrate and for antithrombin III inhibition rate constants, from those of the unmodified enzyme. The 10,000-fold rate enhancement elicited by the addition of heparin to the antithrombin III inhibition reaction, however, is the same. The observed second-order rate constants (k"obs) for antithrombin III inhibition of factor Xa and methylated factor Xa are 3000 and 340 M-1 s-1, respectively, whereas k"obs values for the inhibition of factor Xa or methylated factor Xa with antithrombin III-heparin are 4 X 10(7) and 3 X 10(6) M-1 s-1, respectively. These findings provide direct evidence that the interaction of factor Xa with heparin is not involved in the heparin-enhanced inhibition of this enzyme. |
| doi_str_mv | 10.1021/bi00492a015 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_80145172</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>80145172</sourcerecordid><originalsourceid>FETCH-LOGICAL-a384t-de2258156c5cf933dcc7bd224346cc89fb84f3a7716370a2a94da5b0dd8bbdaa3</originalsourceid><addsrcrecordid>eNptkE1rFTEUhoMo9VpduRayURcyms-ZyVKK2sGighXchZOP4abem9wmGbT_3pQ7VEGzSQ7vk4fDi9BTSl5TwugbEwgRigGh8h7aUMlIJ5SS99GGENJ3TPXkIXpUylUbBRnECTphTIxKig2qU6w-g60hRZxmPLdnyvg74J-hbvHWHyCHiF3yBcdUsU2x5mCW6nFNuG49DnEbTPj3v7nBEGuT5LQ3TTFNU7fqHqMHM-yKf7Lep-jb-3eXZ-fdxecP09nbiw74KGrnPGNypLK30s6Kc2ftYFxbnYve2lHNZhQzh2GgPR8IMFDCgTTEudEYB8BP0Yuj95DT9eJL1ftQrN_tIPq0FD0SKiQdWANfHUGbUynZz_qQwx7yjaZE33as_-q40c9W7WL23t2xa6ktf77mUCzs5gzRhvJHqXp2exrXHblQqv91l0P-ofuBD1JffvmqPwlyzgcq9MfGvzzyYIu-SkuOrbz_bvgb_FWgHQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>80145172</pqid></control><display><type>article</type><title>Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin</title><source>MEDLINE</source><source>ACS Publications</source><creator>Owen, Barbara A ; Owen, Whyte G</creator><creatorcontrib>Owen, Barbara A ; Owen, Whyte G</creatorcontrib><description>Factor Xa modified by reductive methylation (greater than 92%) loses the capacity to bind heparin as determined both by gel chromatography and by sedimentation equilibrium ultracentrifugation. The kinetic properties of methylated factor Xa differ, with respect to KM and Vmax for a synthetic tripeptide substrate and for antithrombin III inhibition rate constants, from those of the unmodified enzyme. The 10,000-fold rate enhancement elicited by the addition of heparin to the antithrombin III inhibition reaction, however, is the same. The observed second-order rate constants (k"obs) for antithrombin III inhibition of factor Xa and methylated factor Xa are 3000 and 340 M-1 s-1, respectively, whereas k"obs values for the inhibition of factor Xa or methylated factor Xa with antithrombin III-heparin are 4 X 10(7) and 3 X 10(6) M-1 s-1, respectively. These findings provide direct evidence that the interaction of factor Xa with heparin is not involved in the heparin-enhanced inhibition of this enzyme.</description><identifier>ISSN: 0006-2960</identifier><identifier>EISSN: 1520-4995</identifier><identifier>DOI: 10.1021/bi00492a015</identifier><identifier>PMID: 2248954</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Antithrombin III - pharmacology ; Biological and medical sciences ; Blood coagulation. Blood cells ; Cattle ; Coagulation factors ; Factor Xa - chemistry ; Factor Xa - metabolism ; Factor Xa Inhibitors ; Fundamental and applied biological sciences. Psychology ; Heparin - metabolism ; Heparin - pharmacology ; In Vitro Techniques ; Kinetics ; Methylation ; Molecular and cellular biology ; Protein Binding</subject><ispartof>Biochemistry (Easton), 1990-10, Vol.29 (40), p.9412-9417</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a384t-de2258156c5cf933dcc7bd224346cc89fb84f3a7716370a2a94da5b0dd8bbdaa3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bi00492a015$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bi00492a015$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2763,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19622222$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2248954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Owen, Barbara A</creatorcontrib><creatorcontrib>Owen, Whyte G</creatorcontrib><title>Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin</title><title>Biochemistry (Easton)</title><addtitle>Biochemistry</addtitle><description>Factor Xa modified by reductive methylation (greater than 92%) loses the capacity to bind heparin as determined both by gel chromatography and by sedimentation equilibrium ultracentrifugation. The kinetic properties of methylated factor Xa differ, with respect to KM and Vmax for a synthetic tripeptide substrate and for antithrombin III inhibition rate constants, from those of the unmodified enzyme. The 10,000-fold rate enhancement elicited by the addition of heparin to the antithrombin III inhibition reaction, however, is the same. The observed second-order rate constants (k"obs) for antithrombin III inhibition of factor Xa and methylated factor Xa are 3000 and 340 M-1 s-1, respectively, whereas k"obs values for the inhibition of factor Xa or methylated factor Xa with antithrombin III-heparin are 4 X 10(7) and 3 X 10(6) M-1 s-1, respectively. These findings provide direct evidence that the interaction of factor Xa with heparin is not involved in the heparin-enhanced inhibition of this enzyme.</description><subject>Animals</subject><subject>Antithrombin III - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood coagulation. Blood cells</subject><subject>Cattle</subject><subject>Coagulation factors</subject><subject>Factor Xa - chemistry</subject><subject>Factor Xa - metabolism</subject><subject>Factor Xa Inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Heparin - metabolism</subject><subject>Heparin - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Kinetics</subject><subject>Methylation</subject><subject>Molecular and cellular biology</subject><subject>Protein Binding</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1rFTEUhoMo9VpduRayURcyms-ZyVKK2sGighXchZOP4abem9wmGbT_3pQ7VEGzSQ7vk4fDi9BTSl5TwugbEwgRigGh8h7aUMlIJ5SS99GGENJ3TPXkIXpUylUbBRnECTphTIxKig2qU6w-g60hRZxmPLdnyvg74J-hbvHWHyCHiF3yBcdUsU2x5mCW6nFNuG49DnEbTPj3v7nBEGuT5LQ3TTFNU7fqHqMHM-yKf7Lep-jb-3eXZ-fdxecP09nbiw74KGrnPGNypLK30s6Kc2ftYFxbnYve2lHNZhQzh2GgPR8IMFDCgTTEudEYB8BP0Yuj95DT9eJL1ftQrN_tIPq0FD0SKiQdWANfHUGbUynZz_qQwx7yjaZE33as_-q40c9W7WL23t2xa6ktf77mUCzs5gzRhvJHqXp2exrXHblQqv91l0P-ofuBD1JffvmqPwlyzgcq9MfGvzzyYIu-SkuOrbz_bvgb_FWgHQ</recordid><startdate>19901001</startdate><enddate>19901001</enddate><creator>Owen, Barbara A</creator><creator>Owen, Whyte G</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19901001</creationdate><title>Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin</title><author>Owen, Barbara A ; Owen, Whyte G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a384t-de2258156c5cf933dcc7bd224346cc89fb84f3a7716370a2a94da5b0dd8bbdaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>Antithrombin III - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood coagulation. Blood cells</topic><topic>Cattle</topic><topic>Coagulation factors</topic><topic>Factor Xa - chemistry</topic><topic>Factor Xa - metabolism</topic><topic>Factor Xa Inhibitors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Heparin - metabolism</topic><topic>Heparin - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Kinetics</topic><topic>Methylation</topic><topic>Molecular and cellular biology</topic><topic>Protein Binding</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Owen, Barbara A</creatorcontrib><creatorcontrib>Owen, Whyte G</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Owen, Barbara A</au><au>Owen, Whyte G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>1990-10-01</date><risdate>1990</risdate><volume>29</volume><issue>40</issue><spage>9412</spage><epage>9417</epage><pages>9412-9417</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>Factor Xa modified by reductive methylation (greater than 92%) loses the capacity to bind heparin as determined both by gel chromatography and by sedimentation equilibrium ultracentrifugation. The kinetic properties of methylated factor Xa differ, with respect to KM and Vmax for a synthetic tripeptide substrate and for antithrombin III inhibition rate constants, from those of the unmodified enzyme. The 10,000-fold rate enhancement elicited by the addition of heparin to the antithrombin III inhibition reaction, however, is the same. The observed second-order rate constants (k"obs) for antithrombin III inhibition of factor Xa and methylated factor Xa are 3000 and 340 M-1 s-1, respectively, whereas k"obs values for the inhibition of factor Xa or methylated factor Xa with antithrombin III-heparin are 4 X 10(7) and 3 X 10(6) M-1 s-1, respectively. These findings provide direct evidence that the interaction of factor Xa with heparin is not involved in the heparin-enhanced inhibition of this enzyme.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>2248954</pmid><doi>10.1021/bi00492a015</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-2960 |
| ispartof | Biochemistry (Easton), 1990-10, Vol.29 (40), p.9412-9417 |
| issn | 0006-2960 1520-4995 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80145172 |
| source | MEDLINE; ACS Publications |
| subjects | Animals Antithrombin III - pharmacology Biological and medical sciences Blood coagulation. Blood cells Cattle Coagulation factors Factor Xa - chemistry Factor Xa - metabolism Factor Xa Inhibitors Fundamental and applied biological sciences. Psychology Heparin - metabolism Heparin - pharmacology In Vitro Techniques Kinetics Methylation Molecular and cellular biology Protein Binding |
| title | Interaction of factor Xa with heparin does not contribute to the inhibition of factor Xa by antithrombin III-heparin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T19%3A04%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interaction%20of%20factor%20Xa%20with%20heparin%20does%20not%20contribute%20to%20the%20inhibition%20of%20factor%20Xa%20by%20antithrombin%20III-heparin&rft.jtitle=Biochemistry%20(Easton)&rft.au=Owen,%20Barbara%20A&rft.date=1990-10-01&rft.volume=29&rft.issue=40&rft.spage=9412&rft.epage=9417&rft.pages=9412-9417&rft.issn=0006-2960&rft.eissn=1520-4995&rft_id=info:doi/10.1021/bi00492a015&rft_dat=%3Cproquest_cross%3E80145172%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=80145172&rft_id=info:pmid/2248954&rfr_iscdi=true |