Aldo-keto reductase

SEE ALSO:

• Hydroxysteroid dehydrogenase

Function

Aldo-keto reductase (AKR) is a protein family which contains enzymes that reduce carbonyl substrates like sugar aldehyde, keto-steroid, keto-prostaglandin, retinal, quinones and lipid peroxidation by-products to primary alcohol^[1]. AKR uses NADP as a cofactor. AKRs contain a conserved catalytic tetrad consisting of Tyr, Asp, Lys and His.

• AKR1B10 reduces aliphatic and aromatic aldehydes. It is expressed in adrenal gland, small intestines and colon.
  
• AKR1B14 is involved in synthesis of prostaglandin F and detoxification of products of lipid peroxidation.
  
• AKR1C4 interconverts steroidal hormone between its active and inactive form^[2].
  
• AKR1C13 involved in detoxification of xenobiotics in the stomach^[3].
  
• AKR1D1 is responsible for the catalysis of 5-β-reduction of bile acid intermediates and steroid hormones carrying a δ(4)-3-one structure.
  

Disease

Mutations in AKR1D1 cause a form of bile acid deficiency which can be fatal in newborns^[4]. AKR1D1 inhibitor Finasteride is used as treatment for benign prostate hyperplasia.

Structural highlights

The active site of AKR1B10 contains the cofactor and a . Water molecules are shown as red spheres.

• are part of the enzyme catalytic tetrad^[5].
• .

3D structures of aldo-keto reductase

Aldo-keto reductase 3D structures