A single amino acid substitution (Leu160His) in cytochrome P 450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin
Identifieur interne : 000A68 ( Istex/Curation ); précédent : 000A67; suivant : 000A69A single amino acid substitution (Leu160His) in cytochrome P 450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin
Auteurs : H. Hadidi [Norvège, Jordanie] ; K. Zahlsen [Norvège] ; J. R. Idle [Norvège] ; S. Cholerton [Royaume-Uni]Source :
- Food and Chemical Toxicology [ 0278-6915 ] ; 1997.
Abstract
Human populations are thought to metabolize coumarin almost exclusively by 7-hydroxylation. We have identified an individual who is homozygous for a single amino acid substitution (Leul60His) in the cytochrome P450 CYP2A6 arising from the variant CYP2A6∗2 allele. On administration of coumarin (2 mg orally) no detectable 7-hydroxycoumarin was excreted in the 0–8-hr urine, rather, approximately 50% of the dose was eliminated as 2-hydroxyphenylacetic acid, the end-product of coumarin 3-hydroxylation. His immediate family members, who were heterozygous for the CYP2A6∗2 allele, excreted little 2-hydroxyphenylacetic acid and mainly 7-hydroxycoumarin, when similarly tested. These findings raise a question regarding human risk evaluations for environmental coumarin exposures, since 7-hydroxylation is regarded as a detoxication pathway, but 3-hydroxylation as the process required to lead to macromolecular covalent binding of coumarin. Persons homozygous for the CYP2A6∗2 allele may constitute 1–25% of various populations.
Url:
DOI: 10.1016/S0278-6915(97)00066-5
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000A68
Links to Exploration step
ISTEX:16EF93B8E34A83E40226DA46C8BB208D6C8AB35BLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>A single amino acid substitution (Leu160His) in cytochrome P 450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin</title>
<author><name sortKey="Hadidi, H" sort="Hadidi, H" uniqKey="Hadidi H" first="H." last="Hadidi">H. Hadidi</name>
<affiliation wicri:level="1"><mods:affiliation>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation>∗ On sabbatical leave from the Jordan University of Science and Technology, Irbid, Jordan.</mods:affiliation>
<country xml:lang="fr">Jordanie</country>
<wicri:regionArea>∗ On sabbatical leave from the Jordan University of Science and Technology, Irbid</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zahlsen, K" sort="Zahlsen, K" uniqKey="Zahlsen K" first="K." last="Zahlsen">K. Zahlsen</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Idle, J R" sort="Idle, J R" uniqKey="Idle J" first="J. R." last="Idle">J. R. Idle</name>
<affiliation><mods:affiliation>Author for correspondence.</mods:affiliation>
<wicri:noCountry code="no comma">Author for correspondence.</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cholerton, S" sort="Cholerton, S" uniqKey="Cholerton S" first="S." last="Cholerton">S. Cholerton</name>
<affiliation wicri:level="1"><mods:affiliation>Pharmacogenetics Research Unit, Department of Pharmacological Sciences, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK</mods:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pharmacogenetics Research Unit, Department of Pharmacological Sciences, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:16EF93B8E34A83E40226DA46C8BB208D6C8AB35B</idno>
<date when="1997" year="1997">1997</date>
<idno type="doi">10.1016/S0278-6915(97)00066-5</idno>
<idno type="url">https://api.istex.fr/document/16EF93B8E34A83E40226DA46C8BB208D6C8AB35B/fulltext/pdf</idno>
<idno type="wicri:Area/Istex/Corpus">000A68</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000A68</idno>
<idno type="wicri:Area/Istex/Curation">000A68</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a">A single amino acid substitution (Leu160His) in cytochrome P 450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin</title>
<author><name sortKey="Hadidi, H" sort="Hadidi, H" uniqKey="Hadidi H" first="H." last="Hadidi">H. Hadidi</name>
<affiliation wicri:level="1"><mods:affiliation>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation>∗ On sabbatical leave from the Jordan University of Science and Technology, Irbid, Jordan.</mods:affiliation>
<country xml:lang="fr">Jordanie</country>
<wicri:regionArea>∗ On sabbatical leave from the Jordan University of Science and Technology, Irbid</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zahlsen, K" sort="Zahlsen, K" uniqKey="Zahlsen K" first="K." last="Zahlsen">K. Zahlsen</name>
<affiliation wicri:level="1"><mods:affiliation>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Idle, J R" sort="Idle, J R" uniqKey="Idle J" first="J. R." last="Idle">J. R. Idle</name>
<affiliation><mods:affiliation>Author for correspondence.</mods:affiliation>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Institute for Cancer Research and Molecular Biology, Norwegian University of Science and Technology, 7005 Trondheim</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><mods:affiliation>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim, Norway</mods:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Medical Genetics, Regional Hospital, Eirik Jarls gate 10, 7006 Trondheim</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cholerton, S" sort="Cholerton, S" uniqKey="Cholerton S" first="S." last="Cholerton">S. Cholerton</name>
<affiliation wicri:level="1"><mods:affiliation>Pharmacogenetics Research Unit, Department of Pharmacological Sciences, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK</mods:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Pharmacogenetics Research Unit, Department of Pharmacological Sciences, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH</wicri:regionArea>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Food and Chemical Toxicology</title>
<title level="j" type="abbrev">FCT</title>
<idno type="ISSN">0278-6915</idno>
<imprint><publisher>ELSEVIER</publisher>
<date type="published" when="1997">1997</date>
<biblScope unit="volume">35</biblScope>
<biblScope unit="issue">9</biblScope>
<biblScope unit="page" from="903">903</biblScope>
<biblScope unit="page" to="907">907</biblScope>
</imprint>
<idno type="ISSN">0278-6915</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0278-6915</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass></textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Human populations are thought to metabolize coumarin almost exclusively by 7-hydroxylation. We have identified an individual who is homozygous for a single amino acid substitution (Leul60His) in the cytochrome P450 CYP2A6 arising from the variant CYP2A6∗2 allele. On administration of coumarin (2 mg orally) no detectable 7-hydroxycoumarin was excreted in the 0–8-hr urine, rather, approximately 50% of the dose was eliminated as 2-hydroxyphenylacetic acid, the end-product of coumarin 3-hydroxylation. His immediate family members, who were heterozygous for the CYP2A6∗2 allele, excreted little 2-hydroxyphenylacetic acid and mainly 7-hydroxycoumarin, when similarly tested. These findings raise a question regarding human risk evaluations for environmental coumarin exposures, since 7-hydroxylation is regarded as a detoxication pathway, but 3-hydroxylation as the process required to lead to macromolecular covalent binding of coumarin. Persons homozygous for the CYP2A6∗2 allele may constitute 1–25% of various populations.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A68 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 000A68 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Istex |étape= Curation |type= RBID |clé= ISTEX:16EF93B8E34A83E40226DA46C8BB208D6C8AB35B |texte= A single amino acid substitution (Leu160His) in cytochrome P 450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin }}
![]() | This area was generated with Dilib version V0.6.31. | ![]() |