Effect of mercury, cadmium, nickel, chromium and zinc on kinetic properties of NADPH-cytochrome P450 reductase purified from leaping mullet ( Liza saliens)
Information on the mechanism of metal ion inhibition of NADPH-cytochrome P450 reductase is limited. The purpose of the present paper was to elucidate in vitro effect of Hg +2, Cd +2, Ni +2, Cr +3 and Zn +2 ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase w...
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Veröffentlicht in: | Toxicology in vitro 2007-04, Vol.21 (3), p.408-416 |
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description | Information on the mechanism of metal ion inhibition of NADPH-cytochrome P450 reductase is limited. The purpose of the present paper was to elucidate in vitro effect of Hg
+2, Cd
+2, Ni
+2, Cr
+3 and Zn
+2 ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase was purified from detergent-solubilized liver microsomes from leaping mullet (
Liza saliens). All of the metal ions caused inhibition of the enzyme activity except Zn
+2. At 50
μM metal concentration, Hg
+2 inhibited the cytochrome P450 reductase activity completely (100%), while, at the same concentrations, Cd
+2, Cr
+3 and Ni
+2 caused 66%, 65% and 37% inhibition, respectively. At 50
μM metal concentration, Zn
+2 had no apparent effect on cytochrome P450 reductase activity. The IC
50 values of HgCl
2, CrCl
3, CdCl
2 and NiCl
2 were estimated to be 0.07
μM, 24
μM, 33
μM and 143
μM, respectively. Of the metal ions tested, Hg
+2 exhibited much higher inhibitory effect at lower concentrations, so it was evidently a more potent inhibitor than the others. All four metal ions displayed noncompetitive type of inhibition mechanism for the purified reductase as analyzed by Dixon plot.
K
i values of Hg
+2, Cr
+3, Cd
+2, and Ni
+2 were calculated from Dixon plots as 0.048
μM, 18
μM, 73
μM and 329
μM, respectively. |
doi_str_mv | 10.1016/j.tiv.2006.10.002 |
format | Article |
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+2, Cd
+2, Ni
+2, Cr
+3 and Zn
+2 ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase was purified from detergent-solubilized liver microsomes from leaping mullet (
Liza saliens). All of the metal ions caused inhibition of the enzyme activity except Zn
+2. At 50
μM metal concentration, Hg
+2 inhibited the cytochrome P450 reductase activity completely (100%), while, at the same concentrations, Cd
+2, Cr
+3 and Ni
+2 caused 66%, 65% and 37% inhibition, respectively. At 50
μM metal concentration, Zn
+2 had no apparent effect on cytochrome P450 reductase activity. The IC
50 values of HgCl
2, CrCl
3, CdCl
2 and NiCl
2 were estimated to be 0.07
μM, 24
μM, 33
μM and 143
μM, respectively. Of the metal ions tested, Hg
+2 exhibited much higher inhibitory effect at lower concentrations, so it was evidently a more potent inhibitor than the others. All four metal ions displayed noncompetitive type of inhibition mechanism for the purified reductase as analyzed by Dixon plot.
K
i values of Hg
+2, Cr
+3, Cd
+2, and Ni
+2 were calculated from Dixon plots as 0.048
μM, 18
μM, 73
μM and 329
μM, respectively.</description><identifier>ISSN: 0887-2333</identifier><identifier>EISSN: 1879-3177</identifier><identifier>DOI: 10.1016/j.tiv.2006.10.002</identifier><identifier>PMID: 17113746</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Cadmium ; Chromium ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - toxicity ; Leaping mullet ( Liza saliens) ; Liver - drug effects ; Liver - enzymology ; Liza saliens ; Mercury ; Metals, Heavy - toxicity ; NADPH-cytochrome P450 reductase ; NADPH-Ferrihemoprotein Reductase - metabolism ; Nickel ; Noncompetitive inhibition ; Smegmamorpha - metabolism ; Water Pollutants, Chemical - toxicity ; Zinc</subject><ispartof>Toxicology in vitro, 2007-04, Vol.21 (3), p.408-416</ispartof><rights>2006 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-d5dc1513b09f4fef2424db61503ece981e3700958ae0831722f08260d5d061e53</citedby><cites>FETCH-LOGICAL-c382t-d5dc1513b09f4fef2424db61503ece981e3700958ae0831722f08260d5d061e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tiv.2006.10.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17113746$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bozcaarmutlu, Azra</creatorcontrib><creatorcontrib>Arinç, Emel</creatorcontrib><title>Effect of mercury, cadmium, nickel, chromium and zinc on kinetic properties of NADPH-cytochrome P450 reductase purified from leaping mullet ( Liza saliens)</title><title>Toxicology in vitro</title><addtitle>Toxicol In Vitro</addtitle><description>Information on the mechanism of metal ion inhibition of NADPH-cytochrome P450 reductase is limited. The purpose of the present paper was to elucidate in vitro effect of Hg
+2, Cd
+2, Ni
+2, Cr
+3 and Zn
+2 ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase was purified from detergent-solubilized liver microsomes from leaping mullet (
Liza saliens). All of the metal ions caused inhibition of the enzyme activity except Zn
+2. At 50
μM metal concentration, Hg
+2 inhibited the cytochrome P450 reductase activity completely (100%), while, at the same concentrations, Cd
+2, Cr
+3 and Ni
+2 caused 66%, 65% and 37% inhibition, respectively. At 50
μM metal concentration, Zn
+2 had no apparent effect on cytochrome P450 reductase activity. The IC
50 values of HgCl
2, CrCl
3, CdCl
2 and NiCl
2 were estimated to be 0.07
μM, 24
μM, 33
μM and 143
μM, respectively. Of the metal ions tested, Hg
+2 exhibited much higher inhibitory effect at lower concentrations, so it was evidently a more potent inhibitor than the others. All four metal ions displayed noncompetitive type of inhibition mechanism for the purified reductase as analyzed by Dixon plot.
K
i values of Hg
+2, Cr
+3, Cd
+2, and Ni
+2 were calculated from Dixon plots as 0.048
μM, 18
μM, 73
μM and 329
μM, respectively.</description><subject>Animals</subject><subject>Cadmium</subject><subject>Chromium</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - toxicity</subject><subject>Leaping mullet ( Liza saliens)</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liza saliens</subject><subject>Mercury</subject><subject>Metals, Heavy - toxicity</subject><subject>NADPH-cytochrome P450 reductase</subject><subject>NADPH-Ferrihemoprotein Reductase - metabolism</subject><subject>Nickel</subject><subject>Noncompetitive inhibition</subject><subject>Smegmamorpha - metabolism</subject><subject>Water Pollutants, Chemical - toxicity</subject><subject>Zinc</subject><issn>0887-2333</issn><issn>1879-3177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1vVCEYhYmxsWP1B7gxrIwmveML3A9uXDW12iaT2oWuCQMvyvR-Cdwm07_in5XrTNKdK8LhnJMcHkLeMFgzYPXH3Tr5hzUHqPN9DcCfkRWTTVsI1jTPyQqkbAouhDglL2PcAUAlObwgp6xhTDRlvSJ_rpxDk-joaI_BzGF_To22vZ_7czp4c49dFn6FcVGoHix99IOh40Dv_YDJGzqFccKQPMal5Pbi8911YfZp_BdCeldWQAPa2SQdkU5z8M6jpS6_0g715IeftJ-7DhN9Tzf-UdOoO49D_PCKnDjdRXx9PM_Ijy9X3y-vi823rzeXF5vCCMlTYStrWMXEFlpXOnS85KXd1qwCgQZbyVA0AG0lNYLMP8O5A8lryDmoGVbijLw79OYpv2eMSfU-Guw6PeA4R8XanC9Fk43sYDRhjDGgU1PwvQ57xUAtRNROZSJqIbJImUjOvD2Wz9se7VPiiCAbPh0MmCc-eAwqmjzfoPUhk1F29P-p_wuINJxF</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Bozcaarmutlu, Azra</creator><creator>Arinç, Emel</creator><general>Elsevier Ltd</general><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>7U7</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>L.G</scope></search><sort><creationdate>20070401</creationdate><title>Effect of mercury, cadmium, nickel, chromium and zinc on kinetic properties of NADPH-cytochrome P450 reductase purified from leaping mullet ( Liza saliens)</title><author>Bozcaarmutlu, Azra ; Arinç, Emel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-d5dc1513b09f4fef2424db61503ece981e3700958ae0831722f08260d5d061e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Cadmium</topic><topic>Chromium</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - toxicity</topic><topic>Leaping mullet ( Liza saliens)</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liza saliens</topic><topic>Mercury</topic><topic>Metals, Heavy - toxicity</topic><topic>NADPH-cytochrome P450 reductase</topic><topic>NADPH-Ferrihemoprotein Reductase - metabolism</topic><topic>Nickel</topic><topic>Noncompetitive inhibition</topic><topic>Smegmamorpha - metabolism</topic><topic>Water Pollutants, Chemical - toxicity</topic><topic>Zinc</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bozcaarmutlu, Azra</creatorcontrib><creatorcontrib>Arinç, Emel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Toxicology in vitro</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bozcaarmutlu, Azra</au><au>Arinç, Emel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of mercury, cadmium, nickel, chromium and zinc on kinetic properties of NADPH-cytochrome P450 reductase purified from leaping mullet ( Liza saliens)</atitle><jtitle>Toxicology in vitro</jtitle><addtitle>Toxicol In Vitro</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>21</volume><issue>3</issue><spage>408</spage><epage>416</epage><pages>408-416</pages><issn>0887-2333</issn><eissn>1879-3177</eissn><abstract>Information on the mechanism of metal ion inhibition of NADPH-cytochrome P450 reductase is limited. The purpose of the present paper was to elucidate in vitro effect of Hg
+2, Cd
+2, Ni
+2, Cr
+3 and Zn
+2 ions on the purified mullet NADPH-cytochrome P450 reductase. NADPH-cytochrome P450 reductase was purified from detergent-solubilized liver microsomes from leaping mullet (
Liza saliens). All of the metal ions caused inhibition of the enzyme activity except Zn
+2. At 50
μM metal concentration, Hg
+2 inhibited the cytochrome P450 reductase activity completely (100%), while, at the same concentrations, Cd
+2, Cr
+3 and Ni
+2 caused 66%, 65% and 37% inhibition, respectively. At 50
μM metal concentration, Zn
+2 had no apparent effect on cytochrome P450 reductase activity. The IC
50 values of HgCl
2, CrCl
3, CdCl
2 and NiCl
2 were estimated to be 0.07
μM, 24
μM, 33
μM and 143
μM, respectively. Of the metal ions tested, Hg
+2 exhibited much higher inhibitory effect at lower concentrations, so it was evidently a more potent inhibitor than the others. All four metal ions displayed noncompetitive type of inhibition mechanism for the purified reductase as analyzed by Dixon plot.
K
i values of Hg
+2, Cr
+3, Cd
+2, and Ni
+2 were calculated from Dixon plots as 0.048
μM, 18
μM, 73
μM and 329
μM, respectively.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>17113746</pmid><doi>10.1016/j.tiv.2006.10.002</doi><tpages>9</tpages></addata></record> |
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subjects | Animals Cadmium Chromium Dose-Response Relationship, Drug Enzyme Inhibitors - toxicity Leaping mullet ( Liza saliens) Liver - drug effects Liver - enzymology Liza saliens Mercury Metals, Heavy - toxicity NADPH-cytochrome P450 reductase NADPH-Ferrihemoprotein Reductase - metabolism Nickel Noncompetitive inhibition Smegmamorpha - metabolism Water Pollutants, Chemical - toxicity Zinc |
title | Effect of mercury, cadmium, nickel, chromium and zinc on kinetic properties of NADPH-cytochrome P450 reductase purified from leaping mullet ( Liza saliens) |
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