Human Cytochrome P450 2C9 and Its Polymorphic Modifications: Electroanalysis, Catalytic Properties, and Approaches to the Regulation of Enzymatic Activity
The electrochemical properties of cytochrome P450 2C9 (CYP2C9) and polymorphic modifications P450 2C9*2 (CYP2C9*2) and P450 2C9*3 (CYP2C9*3) were studied. To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-lik...
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creator | Shumyantseva, Victoria V. Bulko, Tatiana V. Koroleva, Polina I. Shikh, Evgeniya V. Makhova, Anna A. Kisel, Maryia S. Haidukevich, Irina V. Gilep, Andrei A. |
description | The electrochemical properties of cytochrome P450 2C9 (CYP2C9) and polymorphic modifications P450 2C9*2 (CYP2C9*2) and P450 2C9*3 (CYP2C9*3) were studied. To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-like synthetic surfactant (didodecyldimethylammonium bromide (DDAB)). An adequate choice of the type of modified electrode was confirmed by cyclic voltammetry of cytochromes P450 under anaerobic conditions, demonstrating well-defined peaks of reduction and oxidation of the heme iron. The midpoint potential, Emid, of cytochrome P450 2C9 is −0.318 ± 0.01 V, and Emid = −0.324 ± 0.01 V, and Emid = −0.318 ± 0.03 V for allelic variant 2C9*2 and allelic variant 2C9*3, respectively. In the presence of substrate diclofenac under aerobic conditions, cytochrome P450 2C9 and its polymorphic modifications P450 2C9*2 and P450 2C9*3 exhibit catalytic properties. Stimulation of the metabolism of diclofenac by cytochrome P450 2C9 in the presence of antioxidant medications mexidol and taurine was shown. |
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To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-like synthetic surfactant (didodecyldimethylammonium bromide (DDAB)). An adequate choice of the type of modified electrode was confirmed by cyclic voltammetry of cytochromes P450 under anaerobic conditions, demonstrating well-defined peaks of reduction and oxidation of the heme iron. The midpoint potential, Emid, of cytochrome P450 2C9 is −0.318 ± 0.01 V, and Emid = −0.324 ± 0.01 V, and Emid = −0.318 ± 0.03 V for allelic variant 2C9*2 and allelic variant 2C9*3, respectively. In the presence of substrate diclofenac under aerobic conditions, cytochrome P450 2C9 and its polymorphic modifications P450 2C9*2 and P450 2C9*3 exhibit catalytic properties. Stimulation of the metabolism of diclofenac by cytochrome P450 2C9 in the presence of antioxidant medications mexidol and taurine was shown.</description><identifier>ISSN: 2227-9717</identifier><identifier>EISSN: 2227-9717</identifier><identifier>DOI: 10.3390/pr10020383</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Aerobic conditions ; Anaerobic conditions ; Antioxidants ; Catalysis ; Cytochrome ; Cytochrome P450 ; Cytochromes P450 ; Diclofenac ; Drug interactions ; Electrochemical analysis ; Electrodes ; Electrolytic analysis ; Enzymatic activity ; Enzymes ; Experiments ; Heme ; Metabolism ; Mutation ; Nonsteroidal anti-inflammatory drugs ; Oxidation ; Pharmacokinetics ; Proteins ; Software ; Substrates ; Taurine</subject><ispartof>Processes, 2022-02, Vol.10 (2), p.383</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-like synthetic surfactant (didodecyldimethylammonium bromide (DDAB)). An adequate choice of the type of modified electrode was confirmed by cyclic voltammetry of cytochromes P450 under anaerobic conditions, demonstrating well-defined peaks of reduction and oxidation of the heme iron. The midpoint potential, Emid, of cytochrome P450 2C9 is −0.318 ± 0.01 V, and Emid = −0.324 ± 0.01 V, and Emid = −0.318 ± 0.03 V for allelic variant 2C9*2 and allelic variant 2C9*3, respectively. In the presence of substrate diclofenac under aerobic conditions, cytochrome P450 2C9 and its polymorphic modifications P450 2C9*2 and P450 2C9*3 exhibit catalytic properties. Stimulation of the metabolism of diclofenac by cytochrome P450 2C9 in the presence of antioxidant medications mexidol and taurine was shown.</description><subject>Aerobic conditions</subject><subject>Anaerobic conditions</subject><subject>Antioxidants</subject><subject>Catalysis</subject><subject>Cytochrome</subject><subject>Cytochrome P450</subject><subject>Cytochromes P450</subject><subject>Diclofenac</subject><subject>Drug interactions</subject><subject>Electrochemical analysis</subject><subject>Electrodes</subject><subject>Electrolytic analysis</subject><subject>Enzymatic activity</subject><subject>Enzymes</subject><subject>Experiments</subject><subject>Heme</subject><subject>Metabolism</subject><subject>Mutation</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Oxidation</subject><subject>Pharmacokinetics</subject><subject>Proteins</subject><subject>Software</subject><subject>Substrates</subject><subject>Taurine</subject><issn>2227-9717</issn><issn>2227-9717</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpNUNFKw0AQPETBUvviFxz4JlY3t0ku51sJ1RYqFtHncCYXcyXJxbuLED_FrzW1gs7LDsvsMDuEnAdwjSjgprMBAANM8IhMGGN8LnjAj__xUzJzbgcjRIBJFE_I16pvZEvTwZu8sqZRdBtGQFkqqGwLuvaObk09NMZ2lc7pgyl0qXPptWndLV3WKvfWyFbWg9PuiqbSj9SPyq01nbJeq3G7d1p03SjMK-WoN9RXij6pt77-caKmpMv2c2jk_nKRe_2h_XBGTkpZOzX7nVPycrd8TlfzzeP9Ol1s5jkTkZ-HYQFMoIpiiMNChEpgxINIRpAEKgKOHMsSZQJCYBGrUmLMY0BgnIcA8hWn5OLgOwZ875Xz2c70dnzJZSxGhFDgiCm5PKhya5yzqsw6qxtphyyAbF9_9lc_fgO_Jncd</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Shumyantseva, Victoria V.</creator><creator>Bulko, Tatiana V.</creator><creator>Koroleva, Polina I.</creator><creator>Shikh, Evgeniya V.</creator><creator>Makhova, Anna A.</creator><creator>Kisel, Maryia S.</creator><creator>Haidukevich, Irina V.</creator><creator>Gilep, Andrei A.</creator><general>MDPI AG</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>COVID</scope><scope>D1I</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>KB.</scope><scope>LK8</scope><scope>M7P</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><orcidid>https://orcid.org/0000-0003-2802-5747</orcidid><orcidid>https://orcid.org/0000-0003-3432-0064</orcidid></search><sort><creationdate>20220201</creationdate><title>Human Cytochrome P450 2C9 and Its Polymorphic Modifications: Electroanalysis, Catalytic Properties, and Approaches to the Regulation of Enzymatic Activity</title><author>Shumyantseva, Victoria V. ; Bulko, Tatiana V. ; Koroleva, Polina I. ; Shikh, Evgeniya V. ; Makhova, Anna A. ; Kisel, Maryia S. ; Haidukevich, Irina V. ; Gilep, Andrei A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c295t-44d0293e56064d94e935715a5081e507373ff3a80993d6efa3676030277400ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aerobic conditions</topic><topic>Anaerobic conditions</topic><topic>Antioxidants</topic><topic>Catalysis</topic><topic>Cytochrome</topic><topic>Cytochrome P450</topic><topic>Cytochromes P450</topic><topic>Diclofenac</topic><topic>Drug interactions</topic><topic>Electrochemical analysis</topic><topic>Electrodes</topic><topic>Electrolytic analysis</topic><topic>Enzymatic activity</topic><topic>Enzymes</topic><topic>Experiments</topic><topic>Heme</topic><topic>Metabolism</topic><topic>Mutation</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Oxidation</topic><topic>Pharmacokinetics</topic><topic>Proteins</topic><topic>Software</topic><topic>Substrates</topic><topic>Taurine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shumyantseva, Victoria V.</creatorcontrib><creatorcontrib>Bulko, Tatiana V.</creatorcontrib><creatorcontrib>Koroleva, Polina I.</creatorcontrib><creatorcontrib>Shikh, Evgeniya V.</creatorcontrib><creatorcontrib>Makhova, Anna A.</creatorcontrib><creatorcontrib>Kisel, Maryia S.</creatorcontrib><creatorcontrib>Haidukevich, Irina V.</creatorcontrib><creatorcontrib>Gilep, Andrei A.</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>Materials Science Database</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Processes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shumyantseva, Victoria V.</au><au>Bulko, Tatiana V.</au><au>Koroleva, Polina I.</au><au>Shikh, Evgeniya V.</au><au>Makhova, Anna A.</au><au>Kisel, Maryia S.</au><au>Haidukevich, Irina V.</au><au>Gilep, Andrei A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Cytochrome P450 2C9 and Its Polymorphic Modifications: Electroanalysis, Catalytic Properties, and Approaches to the Regulation of Enzymatic Activity</atitle><jtitle>Processes</jtitle><date>2022-02-01</date><risdate>2022</risdate><volume>10</volume><issue>2</issue><spage>383</spage><pages>383-</pages><issn>2227-9717</issn><eissn>2227-9717</eissn><abstract>The electrochemical properties of cytochrome P450 2C9 (CYP2C9) and polymorphic modifications P450 2C9*2 (CYP2C9*2) and P450 2C9*3 (CYP2C9*3) were studied. To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-like synthetic surfactant (didodecyldimethylammonium bromide (DDAB)). An adequate choice of the type of modified electrode was confirmed by cyclic voltammetry of cytochromes P450 under anaerobic conditions, demonstrating well-defined peaks of reduction and oxidation of the heme iron. The midpoint potential, Emid, of cytochrome P450 2C9 is −0.318 ± 0.01 V, and Emid = −0.324 ± 0.01 V, and Emid = −0.318 ± 0.03 V for allelic variant 2C9*2 and allelic variant 2C9*3, respectively. In the presence of substrate diclofenac under aerobic conditions, cytochrome P450 2C9 and its polymorphic modifications P450 2C9*2 and P450 2C9*3 exhibit catalytic properties. Stimulation of the metabolism of diclofenac by cytochrome P450 2C9 in the presence of antioxidant medications mexidol and taurine was shown.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/pr10020383</doi><orcidid>https://orcid.org/0000-0003-2802-5747</orcidid><orcidid>https://orcid.org/0000-0003-3432-0064</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aerobic conditions Anaerobic conditions Antioxidants Catalysis Cytochrome Cytochrome P450 Cytochromes P450 Diclofenac Drug interactions Electrochemical analysis Electrodes Electrolytic analysis Enzymatic activity Enzymes Experiments Heme Metabolism Mutation Nonsteroidal anti-inflammatory drugs Oxidation Pharmacokinetics Proteins Software Substrates Taurine |
title | Human Cytochrome P450 2C9 and Its Polymorphic Modifications: Electroanalysis, Catalytic Properties, and Approaches to the Regulation of Enzymatic Activity |
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