Medium- and short-chain dehydrogenase/reductase gene and protein families

Medium-chain and short-chain dehydrogenases/reductases in retinoid metabolism
Multi-author Review

Abstract.

Retinoic acid (RA), the most active retinoid, is synthesized in two steps from retinol. The first step, oxidation of retinol to retinaldehyde, is catalyzed by cytosolic alcohol dehydrogenases (ADHs) of the medium-chain dehydrogenase/reductase (MDR) superfamily and microsomal retinol dehydrogenases (RDHs) of the short-chain dehydrogenase/reductase (SDR) superfamily. The second step, oxidation of retinaldehyde to RA, is catalyzed by several aldehyde dehydrogenases. ADH1 and ADH2 are the major MDR enzymes in liver retinol detoxification, while ADH3 (less active) and ADH4 (most active) participate in RA generation in tissues. Several NAD+- and NADP+-dependent SDRs are retinoid active. Their in vivo contribution has been demonstrated in the visual cycle (RDH5, RDH12), adult retinoid homeostasis (RDH1) and embryogenesis (RDH10). Km values for most retinoid-active ADHs and RDHs are close to 1 μM or lower, suggesting that they participate physiologically in retinol/retinaldehyde interconversion. Probably none of these enzymes uses retinoids bound to cellular retinol-binding protein, but only free retinoids. The large number of enzymes involved in the two directions of this step, also including aldo-keto reductases, suggests that retinaldehyde levels are strictly regulated.

Keywords.

Alcohol dehydrogenase retinol dehydrogenase retinol retinoic acid retinoid metabolism 

Copyright information

© Birkhäuser Verlag, Basel 2008

Authors and Affiliations

  • X. Parés
    • 1
  • J. Farrés
    • 1
  • N. Kedishvili
    • 2
  • G. Duester
    • 3
  1. 1.Department of Biochemistry and Molecular BiologyUniversitat Autònoma de BarcelonaBellaterra, BarcelonaSpain
  2. 2.Department of Biochemistry and Molecular Genetics, Schools of Medicine and DentistryUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Development and Aging Program, Burnham Institute for Medical ResearchLa JollaUSA

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