Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde

Autores
Diaz Gomez, Maria Isabel; Castro, Gerardo Daniel; Delgado de Layo, A. M. A.; Costantini, Martin Hernan; Castro, Jose Alberto
Año de publicación
2000
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The ability of cytochrome P450 reductase to metabolize ethanol (EtOH) to acetaldehyde (AC) and 1-hydroxyethyl free radicals (1HEt) in anaerobic media was studied. Determination of AC was made by GC-FID analysis of the head space of incubation mixtures. The formation of 1HEt was established by GC-MS analysis of the adduct formed between the radical and the spin trap PBN. Results showed that pure human P450 reductase is able to biotransform EtOH to AC and 1HEt in a NADPH-dependent process under an oxygen-free nitrogen atmosphere. Pure FAD in the presence of NADPH was also able to generate AC and 1HEt from the alcohol. Anaerobic incubation mixtures containing either rat liver microsomes or pure nuclei were also able to biotransform EtOH to AC and 1HEt in the presence of NADPH. These processes were inhibited by antibody against rat liver microsomal P450 reductase. Results suggest that semiquinone forms of the flavin in P450 reductase may biotransform EtOH. These reactions might be of some significance in tissues where the P450 reductase is present in the absence of specific forms of cytochrome P450 known to be involved in EtOH metabolism (e.g. CYP2E1). However the toxicological significance of this enzymatic process remains to be established.
Fil: Diaz Gomez, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
Fil: Delgado de Layo, A. M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Costantini, Martin Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
Materia
1-Hydroxyethyl Free Radical
Acetaldehyde
Anaerobic Biotransformation
Cytochrome P450 Reductase
Ethanol
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/71677
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/71677
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehydeDiaz Gomez, Maria IsabelCastro, Gerardo DanielDelgado de Layo, A. M. A.Costantini, Martin HernanCastro, Jose Alberto1-Hydroxyethyl Free RadicalAcetaldehydeAnaerobic BiotransformationCytochrome P450 ReductaseEthanolhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The ability of cytochrome P450 reductase to metabolize ethanol (EtOH) to acetaldehyde (AC) and 1-hydroxyethyl free radicals (1HEt) in anaerobic media was studied. Determination of AC was made by GC-FID analysis of the head space of incubation mixtures. The formation of 1HEt was established by GC-MS analysis of the adduct formed between the radical and the spin trap PBN. Results showed that pure human P450 reductase is able to biotransform EtOH to AC and 1HEt in a NADPH-dependent process under an oxygen-free nitrogen atmosphere. Pure FAD in the presence of NADPH was also able to generate AC and 1HEt from the alcohol. Anaerobic incubation mixtures containing either rat liver microsomes or pure nuclei were also able to biotransform EtOH to AC and 1HEt in the presence of NADPH. These processes were inhibited by antibody against rat liver microsomal P450 reductase. Results suggest that semiquinone forms of the flavin in P450 reductase may biotransform EtOH. These reactions might be of some significance in tissues where the P450 reductase is present in the absence of specific forms of cytochrome P450 known to be involved in EtOH metabolism (e.g. CYP2E1). However the toxicological significance of this enzymatic process remains to be established.Fil: Diaz Gomez, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Delgado de Layo, A. M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Costantini, Martin Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaElsevier Ireland2000-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/71677Diaz Gomez, Maria Isabel; Castro, Gerardo Daniel; Delgado de Layo, A. M. A.; Costantini, Martin Hernan; Castro, Jose Alberto; Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde; Elsevier Ireland; Toxicology; 154; 1-3; 11-2000; 113-1220300-483XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0300-483X(00)00325-5info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0300483X00003255info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:56Zoai:ri.conicet.gov.ar:11336/71677instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:56.367CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
title Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
spellingShingle Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
Diaz Gomez, Maria Isabel
1-Hydroxyethyl Free Radical
Acetaldehyde
Anaerobic Biotransformation
Cytochrome P450 Reductase
Ethanol
title_short Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
title_full Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
title_fullStr Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
title_full_unstemmed Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
title_sort Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde
dc.creator.none.fl_str_mv Diaz Gomez, Maria Isabel
Castro, Gerardo Daniel
Delgado de Layo, A. M. A.
Costantini, Martin Hernan
Castro, Jose Alberto
author Diaz Gomez, Maria Isabel
author_facet Diaz Gomez, Maria Isabel
Castro, Gerardo Daniel
Delgado de Layo, A. M. A.
Costantini, Martin Hernan
Castro, Jose Alberto
author_role author
author2 Castro, Gerardo Daniel
Delgado de Layo, A. M. A.
Costantini, Martin Hernan
Castro, Jose Alberto
author2_role author
author
author
author
dc.subject.none.fl_str_mv 1-Hydroxyethyl Free Radical
Acetaldehyde
Anaerobic Biotransformation
Cytochrome P450 Reductase
Ethanol
topic 1-Hydroxyethyl Free Radical
Acetaldehyde
Anaerobic Biotransformation
Cytochrome P450 Reductase
Ethanol
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The ability of cytochrome P450 reductase to metabolize ethanol (EtOH) to acetaldehyde (AC) and 1-hydroxyethyl free radicals (1HEt) in anaerobic media was studied. Determination of AC was made by GC-FID analysis of the head space of incubation mixtures. The formation of 1HEt was established by GC-MS analysis of the adduct formed between the radical and the spin trap PBN. Results showed that pure human P450 reductase is able to biotransform EtOH to AC and 1HEt in a NADPH-dependent process under an oxygen-free nitrogen atmosphere. Pure FAD in the presence of NADPH was also able to generate AC and 1HEt from the alcohol. Anaerobic incubation mixtures containing either rat liver microsomes or pure nuclei were also able to biotransform EtOH to AC and 1HEt in the presence of NADPH. These processes were inhibited by antibody against rat liver microsomal P450 reductase. Results suggest that semiquinone forms of the flavin in P450 reductase may biotransform EtOH. These reactions might be of some significance in tissues where the P450 reductase is present in the absence of specific forms of cytochrome P450 known to be involved in EtOH metabolism (e.g. CYP2E1). However the toxicological significance of this enzymatic process remains to be established.
Fil: Diaz Gomez, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
Fil: Delgado de Layo, A. M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Costantini, Martin Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina
Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina
description The ability of cytochrome P450 reductase to metabolize ethanol (EtOH) to acetaldehyde (AC) and 1-hydroxyethyl free radicals (1HEt) in anaerobic media was studied. Determination of AC was made by GC-FID analysis of the head space of incubation mixtures. The formation of 1HEt was established by GC-MS analysis of the adduct formed between the radical and the spin trap PBN. Results showed that pure human P450 reductase is able to biotransform EtOH to AC and 1HEt in a NADPH-dependent process under an oxygen-free nitrogen atmosphere. Pure FAD in the presence of NADPH was also able to generate AC and 1HEt from the alcohol. Anaerobic incubation mixtures containing either rat liver microsomes or pure nuclei were also able to biotransform EtOH to AC and 1HEt in the presence of NADPH. These processes were inhibited by antibody against rat liver microsomal P450 reductase. Results suggest that semiquinone forms of the flavin in P450 reductase may biotransform EtOH. These reactions might be of some significance in tissues where the P450 reductase is present in the absence of specific forms of cytochrome P450 known to be involved in EtOH metabolism (e.g. CYP2E1). However the toxicological significance of this enzymatic process remains to be established.
publishDate 2000
dc.date.none.fl_str_mv 2000-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/71677
Diaz Gomez, Maria Isabel; Castro, Gerardo Daniel; Delgado de Layo, A. M. A.; Costantini, Martin Hernan; Castro, Jose Alberto; Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde; Elsevier Ireland; Toxicology; 154; 1-3; 11-2000; 113-122
0300-483X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/71677
identifier_str_mv Diaz Gomez, Maria Isabel; Castro, Gerardo Daniel; Delgado de Layo, A. M. A.; Costantini, Martin Hernan; Castro, Jose Alberto; Cytochrome P450 reductase-mediated anaerobic biotransformation of ethanol to 1-hydroxyethyl-free radicals and acetaldehyde; Elsevier Ireland; Toxicology; 154; 1-3; 11-2000; 113-122
0300-483X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/S0300-483X(00)00325-5
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0300483X00003255
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842270062753349632
score 13.13397

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