DD3 is a unique enzyme that can specifically catalyze the dehydrogenation of trans-benzenedihydrodiol and trans-naphthalenedihydrodiol.
Human liver contains isoforms of dihydrodiol dehydrogenase (DD1, DD2, DD3 and DD4), which belong to the aldo-oxo reductase/aldo-keto reductase (AKR) superfamily, have 20Alpha- or 3Alpha-hydroxysteroid dehydrogenase (HSD) activity. DD1 is also designated AKR1C1, DDH or DDH1 while DD2 also can be designated AKR1C2, dDD, BABP or DDH2. AKR1C3 and 3Alpha-HSD are alternate designations for DD3, while DD4 also can be called AKR1C4, CD or CHDR. DD1 and DD2 are 20Alpha-HSDs, whereas DD3 and DD4 are the 3Alpha-HSDs. The multiple human cytosolic dihydrodiol dehydrogenases are involved in the metabolism of xenobiotics, such as polycyclic aromatic hydrocarbons, pesticides and steroid hormones, and are responsible for the reduction of ketone-containing drugs by using NADH or NADPH as a cofactor. The 20Alpha-HSD catalyzes the reaction of progesterone to the inactive form 20Alpha-hydroxyprogesterone. The 3Alpha-HSD is a cytosolic, monomeric, NADPH-dependent oxidoreductase that reduces 3-keto-5-dihydrosteroids to their tetrahydro products. DD1 and DD2 are ubiquitously expressed, whereas DD4 mRNA is restricted to the liver.