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.
Abbreviations used: ADH, alcohol dehydrogenase; AKR, aldo–keto reductase; AR, aldose reductase; ARIs, aldose reductase inhibitors; HSI, human small intestine; MDR, medium-chain dehydrogenase/reductase; SDR, short-chain dehydrogenase/reductase.
Present address: Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, U.S.A.