Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism.
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.
Crosas
Bernat
B
Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, E-08193 Bellaterra (Barcelona), Spain.
Hyndman
David J
DJ
Gallego
Oriol
O
Martras
Sílvia
S
Parés
Xavier
X
Flynn
T Geoffrey
TG
Farrés
Jaume
J
D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000449:Aldehyde Reductase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology*; D007700:Kinetics; D012176:Retinoids / Q000378:metabolism*; D013552:Swine
D012176:Retinoids; D000429:Alcohol Oxidoreductases; D000449:Aldehyde Reductase; C084155:alcohol dehydrogenase (NAD(P)+)