Glucuronidation of aliphatic alcohols in human liver microsomes in vitro
The glucuronidation of several short-chained aliphatic alcohols in vitro, with the use of human liver microsomes (HLM) as catalyst, was performed, and the kinetics were studied. The concentrations of the glucuronides were determined by gas chromatography–mass spectrometry after derivatization to the...
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Veröffentlicht in: | Alcohol (Fayetteville, N.Y.) N.Y.), 2004-04, Vol.32 (3), p.187-194 |
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description | The glucuronidation of several short-chained aliphatic alcohols in vitro, with the use of human liver microsomes (HLM) as catalyst, was performed, and the kinetics were studied. The concentrations of the glucuronides were determined by gas chromatography–mass spectrometry after derivatization to the trimethylsilyl compounds. Alcohols from ethanol to pentanols were found to couple with activated glucuronic acid in HLM to a widely varying amount. For analytic reasons the glucuronide of methanol, which is formed after methanol consumption in human beings in vivo, could not be determined. The length of the alkyl chain played the decisive role in the maximum turnover rate of the glucuronidation. The affinity of the alcohols to UDP-glucuronosyltransferase (UDPGT), which catalyzes the glucuronidation reaction, was shown to depend strongly on their structure. Alcohols with a very short alkyl chain and secondary alcohols were glucuronidated much more slowly in comparison with findings for the longer chain primary alcohols and showed less affinity to UDPGT. The alcohols mutually inhibited glucuronidation. However, ethanol inhibited the glucuronidation of isopentanol or n-pentanol only in high concentrations, whereas the two pentanols inhibited each other to a high degree. The glucuronidation of aliphatic alcohols is probably catalyzed by only one of several very similar enzymes of the UDPGT. This finding was indicated by the fact that the Michaelis–Menten constants of the alcohols—with the use of different lots of the HLM from different liver donors—had nearly the same values. |
doi_str_mv | 10.1016/j.alcohol.2004.01.007 |
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The concentrations of the glucuronides were determined by gas chromatography–mass spectrometry after derivatization to the trimethylsilyl compounds. Alcohols from ethanol to pentanols were found to couple with activated glucuronic acid in HLM to a widely varying amount. For analytic reasons the glucuronide of methanol, which is formed after methanol consumption in human beings in vivo, could not be determined. The length of the alkyl chain played the decisive role in the maximum turnover rate of the glucuronidation. The affinity of the alcohols to UDP-glucuronosyltransferase (UDPGT), which catalyzes the glucuronidation reaction, was shown to depend strongly on their structure. Alcohols with a very short alkyl chain and secondary alcohols were glucuronidated much more slowly in comparison with findings for the longer chain primary alcohols and showed less affinity to UDPGT. The alcohols mutually inhibited glucuronidation. However, ethanol inhibited the glucuronidation of isopentanol or n-pentanol only in high concentrations, whereas the two pentanols inhibited each other to a high degree. The glucuronidation of aliphatic alcohols is probably catalyzed by only one of several very similar enzymes of the UDPGT. This finding was indicated by the fact that the Michaelis–Menten constants of the alcohols—with the use of different lots of the HLM from different liver donors—had nearly the same values.</description><identifier>ISSN: 0741-8329</identifier><identifier>EISSN: 1873-6823</identifier><identifier>DOI: 10.1016/j.alcohol.2004.01.007</identifier><identifier>PMID: 15282112</identifier><identifier>CODEN: ALCOEX</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Alcohol ; Alcoholism and acute alcohol poisoning ; Alcohols - chemistry ; Alcohols - metabolism ; Aliphatic alcohols ; Biological and medical sciences ; Chromatography ; Dose-Response Relationship, Drug ; Ethanol ; Experiments ; Glucuronides - metabolism ; Human liver microsomes ; Humans ; Inhibition experiments ; Kinetics of glucuronidation ; Liver ; Medical sciences ; Microbiology ; Microsomes, Liver - metabolism ; Toxicology ; UDPGT</subject><ispartof>Alcohol (Fayetteville, N.Y.), 2004-04, Vol.32 (3), p.187-194</ispartof><rights>2004 Elsevier Inc.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-b3ea7c9fe4e4e24a156197dd960a94eab54d89e072e3514ba4aac034b8843c7d3</citedby><cites>FETCH-LOGICAL-c450t-b3ea7c9fe4e4e24a156197dd960a94eab54d89e072e3514ba4aac034b8843c7d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1027376612?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16042433$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15282112$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jurowich, Sabine</creatorcontrib><creatorcontrib>Sticht, Guido</creatorcontrib><creatorcontrib>Käferstein, Herbert</creatorcontrib><title>Glucuronidation of aliphatic alcohols in human liver microsomes in vitro</title><title>Alcohol (Fayetteville, N.Y.)</title><addtitle>Alcohol</addtitle><description>The glucuronidation of several short-chained aliphatic alcohols in vitro, with the use of human liver microsomes (HLM) as catalyst, was performed, and the kinetics were studied. The concentrations of the glucuronides were determined by gas chromatography–mass spectrometry after derivatization to the trimethylsilyl compounds. Alcohols from ethanol to pentanols were found to couple with activated glucuronic acid in HLM to a widely varying amount. For analytic reasons the glucuronide of methanol, which is formed after methanol consumption in human beings in vivo, could not be determined. The length of the alkyl chain played the decisive role in the maximum turnover rate of the glucuronidation. The affinity of the alcohols to UDP-glucuronosyltransferase (UDPGT), which catalyzes the glucuronidation reaction, was shown to depend strongly on their structure. Alcohols with a very short alkyl chain and secondary alcohols were glucuronidated much more slowly in comparison with findings for the longer chain primary alcohols and showed less affinity to UDPGT. The alcohols mutually inhibited glucuronidation. However, ethanol inhibited the glucuronidation of isopentanol or n-pentanol only in high concentrations, whereas the two pentanols inhibited each other to a high degree. The glucuronidation of aliphatic alcohols is probably catalyzed by only one of several very similar enzymes of the UDPGT. This finding was indicated by the fact that the Michaelis–Menten constants of the alcohols—with the use of different lots of the HLM from different liver donors—had nearly the same values.</description><subject>Alcohol</subject><subject>Alcoholism and acute alcohol poisoning</subject><subject>Alcohols - chemistry</subject><subject>Alcohols - metabolism</subject><subject>Aliphatic alcohols</subject><subject>Biological and medical sciences</subject><subject>Chromatography</subject><subject>Dose-Response Relationship, Drug</subject><subject>Ethanol</subject><subject>Experiments</subject><subject>Glucuronides - metabolism</subject><subject>Human liver microsomes</subject><subject>Humans</subject><subject>Inhibition experiments</subject><subject>Kinetics of glucuronidation</subject><subject>Liver</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Microsomes, Liver - metabolism</subject><subject>Toxicology</subject><subject>UDPGT</subject><issn>0741-8329</issn><issn>1873-6823</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkU1r3DAQhkVpaTZpf0KCoSQ3u6MPS_aphJCPQqCX9ixkecxqka2tZC_k31ebNQR6CToIoWfemXlfQi4pVBSo_L6rjLdhG3zFAEQFtAJQH8iGNoqXsmH8I9mAErRsOGvPyHlKO8iEUu1nckZr1jBK2YY8PfrFLjFMrjezC1MRhsJ4t9_mly3WFqlwU7FdRjMV3h0wFqOzMaQw4uvPwc0xfCGfBuMTfl3vC_Ln4f733VP5_Ovx593tc2lFDXPZcTTKtgOKfJgwtJa0VX3fSjCtQNPVom9aBMWQ11R0RhhjgYuuaQS3qucX5Oaku4_h74Jp1qNLFr03E4YlaSmVBMnZuyBtgIPiPIPf_gN3YYlTXkJTYIorKelRrj5Rx81TxEHvoxtNfMmQPiaid3q1Sx8T0UB19jvXXa3qSzdi_1a1RpCB6xUwyRo_RDNZl944CYKJ1zF_nDjM7h4cRp2sw8li7yLaWffBvTPKPz5Lq2o</recordid><startdate>20040401</startdate><enddate>20040401</enddate><creator>Jurowich, Sabine</creator><creator>Sticht, Guido</creator><creator>Käferstein, Herbert</creator><general>Elsevier Inc</general><general>Elsevier Science</general><general>Elsevier Limited</general><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>0-V</scope><scope>3V.</scope><scope>7QG</scope><scope>7RV</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AM</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGRYB</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K7.</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0O</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20040401</creationdate><title>Glucuronidation of aliphatic alcohols in human liver microsomes in vitro</title><author>Jurowich, Sabine ; Sticht, Guido ; Käferstein, Herbert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-b3ea7c9fe4e4e24a156197dd960a94eab54d89e072e3514ba4aac034b8843c7d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Alcohol</topic><topic>Alcoholism and acute alcohol poisoning</topic><topic>Alcohols - chemistry</topic><topic>Alcohols - metabolism</topic><topic>Aliphatic alcohols</topic><topic>Biological and medical sciences</topic><topic>Chromatography</topic><topic>Dose-Response Relationship, Drug</topic><topic>Ethanol</topic><topic>Experiments</topic><topic>Glucuronides - metabolism</topic><topic>Human liver microsomes</topic><topic>Humans</topic><topic>Inhibition experiments</topic><topic>Kinetics of glucuronidation</topic><topic>Liver</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Microsomes, Liver - metabolism</topic><topic>Toxicology</topic><topic>UDPGT</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jurowich, Sabine</creatorcontrib><creatorcontrib>Sticht, Guido</creatorcontrib><creatorcontrib>Käferstein, Herbert</creatorcontrib><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>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Criminal Justice Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Criminology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Criminal Justice</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Alcohol (Fayetteville, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jurowich, Sabine</au><au>Sticht, Guido</au><au>Käferstein, Herbert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucuronidation of aliphatic alcohols in human liver microsomes in vitro</atitle><jtitle>Alcohol (Fayetteville, N.Y.)</jtitle><addtitle>Alcohol</addtitle><date>2004-04-01</date><risdate>2004</risdate><volume>32</volume><issue>3</issue><spage>187</spage><epage>194</epage><pages>187-194</pages><issn>0741-8329</issn><eissn>1873-6823</eissn><coden>ALCOEX</coden><abstract>The glucuronidation of several short-chained aliphatic alcohols in vitro, with the use of human liver microsomes (HLM) as catalyst, was performed, and the kinetics were studied. The concentrations of the glucuronides were determined by gas chromatography–mass spectrometry after derivatization to the trimethylsilyl compounds. Alcohols from ethanol to pentanols were found to couple with activated glucuronic acid in HLM to a widely varying amount. For analytic reasons the glucuronide of methanol, which is formed after methanol consumption in human beings in vivo, could not be determined. The length of the alkyl chain played the decisive role in the maximum turnover rate of the glucuronidation. The affinity of the alcohols to UDP-glucuronosyltransferase (UDPGT), which catalyzes the glucuronidation reaction, was shown to depend strongly on their structure. Alcohols with a very short alkyl chain and secondary alcohols were glucuronidated much more slowly in comparison with findings for the longer chain primary alcohols and showed less affinity to UDPGT. The alcohols mutually inhibited glucuronidation. However, ethanol inhibited the glucuronidation of isopentanol or n-pentanol only in high concentrations, whereas the two pentanols inhibited each other to a high degree. The glucuronidation of aliphatic alcohols is probably catalyzed by only one of several very similar enzymes of the UDPGT. This finding was indicated by the fact that the Michaelis–Menten constants of the alcohols—with the use of different lots of the HLM from different liver donors—had nearly the same values.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15282112</pmid><doi>10.1016/j.alcohol.2004.01.007</doi><tpages>8</tpages></addata></record> |
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subjects | Alcohol Alcoholism and acute alcohol poisoning Alcohols - chemistry Alcohols - metabolism Aliphatic alcohols Biological and medical sciences Chromatography Dose-Response Relationship, Drug Ethanol Experiments Glucuronides - metabolism Human liver microsomes Humans Inhibition experiments Kinetics of glucuronidation Liver Medical sciences Microbiology Microsomes, Liver - metabolism Toxicology UDPGT |
title | Glucuronidation of aliphatic alcohols in human liver microsomes in vitro |
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