The use of intramolecular isotope effects to distinguish between deprotonation and hydrogen atom abstraction mechanisms in cytochrome P-450- and peroxidase-catalyzed N-demethylation reactions
Intramolecular isotope effects were determined for the N-demethylation of N-methyl-N-trideuteriomethylaniline catalyzed by two isozymes of cytochrome P-450 and several peroxidases in order to differentiate between deprotonation and hydrogen atom abstraction steps. Lactoperoxidase, hemoglobin, myoglo...
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| Veröffentlicht in: | The Journal of biological chemistry 1983-12, Vol.258 (23), p.14445-14449 |
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| container_title | The Journal of biological chemistry |
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| creator | Miwa, G T Walsh, J S Kedderis, G L Hollenberg, P F |
| description | Intramolecular isotope effects were determined for the N-demethylation of N-methyl-N-trideuteriomethylaniline catalyzed by two isozymes of cytochrome P-450 and several peroxidases in order to differentiate between deprotonation and hydrogen atom abstraction steps. Lactoperoxidase, hemoglobin, myoglobin, and two isozymes of horseradish peroxidase catalyzed the hydroperoxide-dependent N-demethylation at initial rates ranging from 20 to 1700 min-1. These hemeproteins exhibited large and comparable intramolecular isotope effects (kH/kD = 8.6 to 10.1). In contrast, two isozymes of cytochrome P-450 as well as chloroperoxidase (v = 1.5 to 1700 min-1) gave low isotope effects (kH/kD = 1.7 to 3.1) under identical conditions. Catalase exhibited an intermediate intramolecular isotope effect (kH/kD = 5.4). These results have been interpreted to indicate that most of the hemeproteins investigated catalyze N-demethylation reactions via alpha-carbon hydrogen atom abstraction, while the reactions catalyzed by cytochrome P-450 and chloroperoxidase proceed via alpha-carbon deprotonation. |
| doi_str_mv | 10.1016/S0021-9258(17)43882-8 |
| format | Article |
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Lactoperoxidase, hemoglobin, myoglobin, and two isozymes of horseradish peroxidase catalyzed the hydroperoxide-dependent N-demethylation at initial rates ranging from 20 to 1700 min-1. These hemeproteins exhibited large and comparable intramolecular isotope effects (kH/kD = 8.6 to 10.1). In contrast, two isozymes of cytochrome P-450 as well as chloroperoxidase (v = 1.5 to 1700 min-1) gave low isotope effects (kH/kD = 1.7 to 3.1) under identical conditions. Catalase exhibited an intermediate intramolecular isotope effect (kH/kD = 5.4). These results have been interpreted to indicate that most of the hemeproteins investigated catalyze N-demethylation reactions via alpha-carbon hydrogen atom abstraction, while the reactions catalyzed by cytochrome P-450 and chloroperoxidase proceed via alpha-carbon deprotonation.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(17)43882-8</identifier><identifier>PMID: 6643495</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Analytical, structural and metabolic biochemistry ; Animals ; Biological and medical sciences ; Cytochrome P-450 Enzyme System - metabolism ; Enzymes and enzyme inhibitors ; Fundamental and applied biological sciences. Psychology ; Hemeproteins - metabolism ; Hemoglobins - metabolism ; Horseradish Peroxidase - metabolism ; Isoenzymes - metabolism ; Kinetics ; Lactoperoxidase - metabolism ; Myoglobin - metabolism ; Oxidoreductases ; Peroxidases - metabolism ; Rats</subject><ispartof>The Journal of biological chemistry, 1983-12, Vol.258 (23), p.14445-14449</ispartof><rights>1983 © 1983 ASBMB. 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Lactoperoxidase, hemoglobin, myoglobin, and two isozymes of horseradish peroxidase catalyzed the hydroperoxide-dependent N-demethylation at initial rates ranging from 20 to 1700 min-1. These hemeproteins exhibited large and comparable intramolecular isotope effects (kH/kD = 8.6 to 10.1). In contrast, two isozymes of cytochrome P-450 as well as chloroperoxidase (v = 1.5 to 1700 min-1) gave low isotope effects (kH/kD = 1.7 to 3.1) under identical conditions. Catalase exhibited an intermediate intramolecular isotope effect (kH/kD = 5.4). These results have been interpreted to indicate that most of the hemeproteins investigated catalyze N-demethylation reactions via alpha-carbon hydrogen atom abstraction, while the reactions catalyzed by cytochrome P-450 and chloroperoxidase proceed via alpha-carbon deprotonation.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hemeproteins - metabolism</subject><subject>Hemoglobins - metabolism</subject><subject>Horseradish Peroxidase - metabolism</subject><subject>Isoenzymes - metabolism</subject><subject>Kinetics</subject><subject>Lactoperoxidase - metabolism</subject><subject>Myoglobin - metabolism</subject><subject>Oxidoreductases</subject><subject>Peroxidases - metabolism</subject><subject>Rats</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1983</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhSMEKtPCI1TyAiG6CNiOkzgrVFX8SRUgUSR2lmPfTIySePB1KOHleDU8mdGIHd54cb5zj31Pll0y-pJRVr36QilnecNL-YLVV6KQkufyQbZhVBZ5UbJvD7PNCXmcnSN-p-mIhp1lZ1UlCtGUm-zPXQ9kRiC-I26KQY9-ADMPOhCHPvodEOg6MBFJ9MQ6jG7azg570kK8B5iIhV1I4KSj8xPRkyX9YoPfJklHPxLdYhprVnUE0-vJ4YgpjJgletMHPwL5nIuS5qt7B8H_clYj5EZHPSy_wZKPuYURYr8Mh5gAh4n4JHvU6QHh6fG-yL6-fXN38z6__fTuw831bW5EI2XeyBq6qmlYK7W2pS4pLxvKacPKtiooB86kASE7oF1hJa8rXUEBtTWQZFoUF9nzw9z02R8zYFSjQwPDoCfwMypJ66rmK1geQBM8YoBO7YIbdVgUo2pfnFqLU_tWFKvVWpySyXd5DJjbEezJdWwq6c-Oukajhy7oyTg8YU0pmOD_YL3b9vcugGpdWjKMap_HC8WEEHvs9QGDtLOfDoJC42AyYJPFRGW9-897_wJx_8Ur</recordid><startdate>19831210</startdate><enddate>19831210</enddate><creator>Miwa, G T</creator><creator>Walsh, J S</creator><creator>Kedderis, G L</creator><creator>Hollenberg, P F</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>19831210</creationdate><title>The use of intramolecular isotope effects to distinguish between deprotonation and hydrogen atom abstraction mechanisms in cytochrome P-450- and peroxidase-catalyzed N-demethylation reactions</title><author>Miwa, G T ; Walsh, J S ; Kedderis, G L ; Hollenberg, P F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4988-987ef6991b8aad5a50259020915b6302e218ce48fe0f3d8276a6e3e7dce630033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1983</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hemeproteins - metabolism</topic><topic>Hemoglobins - metabolism</topic><topic>Horseradish Peroxidase - metabolism</topic><topic>Isoenzymes - metabolism</topic><topic>Kinetics</topic><topic>Lactoperoxidase - metabolism</topic><topic>Myoglobin - metabolism</topic><topic>Oxidoreductases</topic><topic>Peroxidases - metabolism</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miwa, G T</creatorcontrib><creatorcontrib>Walsh, J S</creatorcontrib><creatorcontrib>Kedderis, G L</creatorcontrib><creatorcontrib>Hollenberg, P F</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miwa, G T</au><au>Walsh, J S</au><au>Kedderis, G L</au><au>Hollenberg, P F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The use of intramolecular isotope effects to distinguish between deprotonation and hydrogen atom abstraction mechanisms in cytochrome P-450- and peroxidase-catalyzed N-demethylation reactions</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1983-12-10</date><risdate>1983</risdate><volume>258</volume><issue>23</issue><spage>14445</spage><epage>14449</epage><pages>14445-14449</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>Intramolecular isotope effects were determined for the N-demethylation of N-methyl-N-trideuteriomethylaniline catalyzed by two isozymes of cytochrome P-450 and several peroxidases in order to differentiate between deprotonation and hydrogen atom abstraction steps. Lactoperoxidase, hemoglobin, myoglobin, and two isozymes of horseradish peroxidase catalyzed the hydroperoxide-dependent N-demethylation at initial rates ranging from 20 to 1700 min-1. These hemeproteins exhibited large and comparable intramolecular isotope effects (kH/kD = 8.6 to 10.1). In contrast, two isozymes of cytochrome P-450 as well as chloroperoxidase (v = 1.5 to 1700 min-1) gave low isotope effects (kH/kD = 1.7 to 3.1) under identical conditions. Catalase exhibited an intermediate intramolecular isotope effect (kH/kD = 5.4). These results have been interpreted to indicate that most of the hemeproteins investigated catalyze N-demethylation reactions via alpha-carbon hydrogen atom abstraction, while the reactions catalyzed by cytochrome P-450 and chloroperoxidase proceed via alpha-carbon deprotonation.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>6643495</pmid><doi>10.1016/S0021-9258(17)43882-8</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 1983-12, Vol.258 (23), p.14445-14449 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Analytical, structural and metabolic biochemistry Animals Biological and medical sciences Cytochrome P-450 Enzyme System - metabolism Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Hemeproteins - metabolism Hemoglobins - metabolism Horseradish Peroxidase - metabolism Isoenzymes - metabolism Kinetics Lactoperoxidase - metabolism Myoglobin - metabolism Oxidoreductases Peroxidases - metabolism Rats |
| title | The use of intramolecular isotope effects to distinguish between deprotonation and hydrogen atom abstraction mechanisms in cytochrome P-450- and peroxidase-catalyzed N-demethylation reactions |
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