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

Biochem J. 2003 Aug 1;373(Pt 3):973-9. doi: 10.1042/BJ20021818.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / chemistry
  • Alcohol Oxidoreductases / metabolism*
  • Aldehyde Reductase / chemistry
  • Aldehyde Reductase / metabolism*
  • Animals
  • Binding Sites
  • Chromatography, High Pressure Liquid
  • Humans
  • Intestine, Small / enzymology*
  • Kinetics
  • Retinoids / metabolism*
  • Swine


  • Retinoids
  • Alcohol Oxidoreductases
  • Aldehyde Reductase
  • alcohol dehydrogenase (NAD(P)+)