{"doi":"10.1042/bj20021818","title":"Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism","abstract":"<jats:p>Aldo–keto reductases (AKRs) are NAD(P)H-dependent oxidoreductases that catalyse the reduction of a variety of carbonyl compounds, such as carbohydrates, aliphatic and aromatic aldehydes and steroids. We have studied the retinal reductase activity of human aldose reductase (AR), human small-intestine (HSI) AR and pig aldehyde reductase. Human AR and HSI AR were very efficient in the reduction of all-trans-, 9-cis- and 13-cis-retinal (kcat/Km=1100–10300 mM−1·min−1), constituting the first cytosolic NADP(H)-dependent retinal reductases described in humans. Aldehyde reductase showed no activity with these retinal isomers. Glucose was a poor inhibitor (Ki=80 mM) of retinal reductase activity of human AR, whereas tolrestat, a classical AKR inhibitor used pharmacologically to treat diabetes, inhibited retinal reduction by human AR and HSI AR. All-trans-retinoic acid failed to inhibit both enzymes. In this paper we present the AKRs as an emergent superfamily of retinal-active enzymes, putatively involved in the regulation of retinoid biological activity through the assimilation of retinoids from β-carotene and the control of retinal bioavailability.</jats:p>","journal":"Biochemical Journal","year":2003,"id":685892,"datarank":0.7640625301210144,"base_score":5.093750200806762,"endowment":5.093750200806762,"self_citation_contribution":0.7640625301210144,"citation_network_contribution":0.0,"self_endowment_contribution":0.7640625301210144,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":162,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1791970,"name":"David J. 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Human AR and HSI AR were very efficient in the reduction of all-trans-, 9-cis- and 13-cis-retinal (kcat/Km=1100–10300 mM−1·min−1), constituting the first cytosolic NADP(H)-dependent retinal reductases described in humans. Aldehyde reductase showed no activity with these retinal isomers. Glucose was a poor inhibitor (Ki=80 mM) of retinal reductase activity of human AR, whereas tolrestat, a classical AKR inhibitor used pharmacologically to treat diabetes, inhibited retinal reduction by human AR and HSI AR. All-trans-retinoic acid failed to inhibit both enzymes. In this paper we present the AKRs as an emergent superfamily of retinal-active enzymes, putatively involved in the regulation of retinoid biological activity through the assimilation of retinoids from β-carotene and the control of retinal bioavailability.</jats:p>","is_dataset_classified":null,"base_score":5.093750200806762,"endowment":5.093750200806762,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12732097","pmcid":"PMC1223539","openalex_id":"https://openalex.org/W2126243275","authors":[],"funders":[],"total_grants":0,"fwci":1.3768,"citation_percentile":0.7906694,"influential_citations":0,"citation_trend":[{"year":2012,"count":16},{"year":2013,"count":13},{"year":2014,"count":8},{"year":2015,"count":4},{"year":2016,"count":12},{"year":2018,"count":7},{"year":2019,"count":2},{"year":2020,"count":2},{"year":2021,"count":10},{"year":2022,"count":7},{"year":2023,"count":1},{"year":2024,"count":6},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://portlandpress.com/biochemj/article-pdf/373/3/973/712403/bj3730973.pdf","host_type":"journal"},{"url":"https://portlandpress.com/biochemj/article-pdf/373/3/973/712403/bj3730973.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj20021818","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12732097","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1223539","host_type":"repository"}],"fields_of_study":["Aldose Reductase and Taurine","Heme Oxygenase-1 and Carbon Monoxide","Prenatal Substance Exposure Effects","Alcohol Oxidoreductases","Aldehyde Reductase","Animals","Binding Sites","Chromatography, High Pressure Liquid","Humans","Intestine, Small","Kinetics","Retinoids","Swine"],"mesh_terms":["Alcohol Oxidoreductases","Aldehyde Reductase","Animals","Binding Sites","Chromatography, High Pressure Liquid","Humans","Intestine, Small","Kinetics","Retinoids","Swine"],"keywords":["Aldose reductase","Aldo-keto reductase","Aldehyde Reductase","Biochemistry","Reductase","Retinal","Aldose reductase inhibitor","Biology","NAD+ kinase","7-Dehydrocholesterol reductase","Retinaldehyde","Enzyme","Chemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T17:57:55.233577Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}