Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism
| Autor: | Bernat Crosas, Sílvia Martras, Jaume Farrés, T. Geoffrey Flynn, David Hyndman, Xavier Parés, Oriol Gallego |
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| Rok vydání: | 2003 |
| Předmět: |
Tolrestat
Swine medicine.drug_class Retinoic acid Biology Biochemistry Retinoids chemistry.chemical_compound Aldehyde Reductase Intestine Small medicine Animals Humans Retinoid Molecular Biology Chromatography High Pressure Liquid Aldose reductase Binding Sites Aldo-Keto Reductase Family 1 member B10 Retinal Cell Biology Alcohol Oxidoreductases Kinetics chemistry NAD+ kinase Research Article |
| Zdroj: | Biochemical Journal. 373:973-979 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20021818 |
| Popis: | 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 ( k (cat)/ K (m)=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 ( K (i)=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 beta-carotene and the control of retinal bioavailability. |
| Databáze: | OpenAIRE |
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