Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling

Several aldo-keto reductase (AKR) enzymes from subfamilies 1B and 1C show retinaldehyde reductase activity, having low K and k values. Only AKR1B10 and 1B12, with all- trans -retinaldehyde, and AKR1C3, with 9- cis -retinaldehyde, display high catalytic efficiency. Major structural determinants for r...

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Autores: Ruiz, F. Xavier, Porte Orduna, Sergio, Parés i Casasampera, Xavier|||0000-0002-5071-9465, Farrés, Jaume|||0000-0001-9069-3987
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:184830
Acceso en línea:https://ddd.uab.cat/record/184830
https://dx.doi.org/urn:doi:10.3389/fphar.2012.00058
Access Level:acceso abierto
Palabra clave:Aldo-keto reductase
Retinaldehyde
Retinoic acid
Retinol
Cancer
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spelling Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and SignalingRuiz, F. XavierPorte Orduna, SergioParés i Casasampera, Xavier|||0000-0002-5071-9465Farrés, Jaume|||0000-0001-9069-3987Aldo-keto reductaseRetinaldehydeRetinoic acidRetinolCancerSeveral aldo-keto reductase (AKR) enzymes from subfamilies 1B and 1C show retinaldehyde reductase activity, having low K and k values. Only AKR1B10 and 1B12, with all- trans -retinaldehyde, and AKR1C3, with 9- cis -retinaldehyde, display high catalytic efficiency. Major structural determinants for retinaldehyde isomer specificity are located in the external loops (A and C for AKR1B10, and B for AKR1C3), as assessed by site-directed mutagenesis and molecular dynamics. Cellular models have shown that AKR1B and 1C enzymes are well suited to work in vivo as retinaldehyde reductases and to regulate retinoic acid (RA) biosynthesis at hormone pre-receptor level. An additional physiological role for the retinaldehyde reductase activity of these enzymes, consistent with their tissue localization, is their participation in β-carotene absorption. Retinaldehyde metabolism may be subjected to subcellular compartmentalization, based on enzyme localization. While retinaldehyde oxidation to RA takes place in the cytosol, reduction to retinol could take place in the cytosol by AKRs or in the membranes of endoplasmic reticulum by microsomal retinaldehyde reductases. Upregulation of some AKR1 enzymes in different cancer types may be linked to their induction by oxidative stress and to their participation in different signaling pathways related to cell proliferation. AKR1B10 and AKR1C3, through their retinaldehyde reductase activity, trigger a decrease in the RA biosynthesis flow, resulting in RA deprivation and consequently lower differentiation, with an increased cancer risk in target tissues. Rational design of selective AKR inhibitors could lead to development of novel drugs for cancer treatment as well as reduction of chemotherapeutic drug resistance. 22012-01-0120122012-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/184830https://dx.doi.org/urn:doi:10.3389/fphar.2012.00058reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2008-02945Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2011-24176Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-795open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1848302026-06-06T12:50:31Z
dc.title.none.fl_str_mv Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
title Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
spellingShingle Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
Ruiz, F. Xavier
Aldo-keto reductase
Retinaldehyde
Retinoic acid
Retinol
Cancer
title_short Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
title_full Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
title_fullStr Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
title_full_unstemmed Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
title_sort Biological Role of Aldo-Keto Reductases in Retinoic Acid Biosynthesis and Signaling
dc.creator.none.fl_str_mv Ruiz, F. Xavier
Porte Orduna, Sergio
Parés i Casasampera, Xavier|||0000-0002-5071-9465
Farrés, Jaume|||0000-0001-9069-3987
author Ruiz, F. Xavier
author_facet Ruiz, F. Xavier
Porte Orduna, Sergio
Parés i Casasampera, Xavier|||0000-0002-5071-9465
Farrés, Jaume|||0000-0001-9069-3987
author_role author
author2 Porte Orduna, Sergio
Parés i Casasampera, Xavier|||0000-0002-5071-9465
Farrés, Jaume|||0000-0001-9069-3987
author2_role author
author
author
dc.subject.none.fl_str_mv Aldo-keto reductase
Retinaldehyde
Retinoic acid
Retinol
Cancer
topic Aldo-keto reductase
Retinaldehyde
Retinoic acid
Retinol
Cancer
description Several aldo-keto reductase (AKR) enzymes from subfamilies 1B and 1C show retinaldehyde reductase activity, having low K and k values. Only AKR1B10 and 1B12, with all- trans -retinaldehyde, and AKR1C3, with 9- cis -retinaldehyde, display high catalytic efficiency. Major structural determinants for retinaldehyde isomer specificity are located in the external loops (A and C for AKR1B10, and B for AKR1C3), as assessed by site-directed mutagenesis and molecular dynamics. Cellular models have shown that AKR1B and 1C enzymes are well suited to work in vivo as retinaldehyde reductases and to regulate retinoic acid (RA) biosynthesis at hormone pre-receptor level. An additional physiological role for the retinaldehyde reductase activity of these enzymes, consistent with their tissue localization, is their participation in β-carotene absorption. Retinaldehyde metabolism may be subjected to subcellular compartmentalization, based on enzyme localization. While retinaldehyde oxidation to RA takes place in the cytosol, reduction to retinol could take place in the cytosol by AKRs or in the membranes of endoplasmic reticulum by microsomal retinaldehyde reductases. Upregulation of some AKR1 enzymes in different cancer types may be linked to their induction by oxidative stress and to their participation in different signaling pathways related to cell proliferation. AKR1B10 and AKR1C3, through their retinaldehyde reductase activity, trigger a decrease in the RA biosynthesis flow, resulting in RA deprivation and consequently lower differentiation, with an increased cancer risk in target tissues. Rational design of selective AKR inhibitors could lead to development of novel drugs for cancer treatment as well as reduction of chemotherapeutic drug resistance.
publishDate 2012
dc.date.none.fl_str_mv 2
2012-01-01
2012
2012-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/184830
https://dx.doi.org/urn:doi:10.3389/fphar.2012.00058
url https://ddd.uab.cat/record/184830
https://dx.doi.org/urn:doi:10.3389/fphar.2012.00058
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2008-02945
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2011-24176
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-795
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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