Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism

Author:

CROSAS Bernat12,HYNDMAN David J.2,GALLEGO Oriol1,MARTRAS Sílvia1,PARÉS Xavier1,FLYNN T. Geoffrey2,FARRÉS Jaume1

Affiliation:

1. Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, E-08193 Bellaterra (Barcelona), Spain

2. Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6

Abstract

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.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

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