Function: Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
Catalytic activity: Trans-1,2-dihydrobenzene-1,2-diol + NADP+ = catechol + NADPH.A 3-alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H.(5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH.Testosterone + NAD+ = androstenedione + NADH.Testosterone + NADP+ = androst-4-ene-3,17-dione + NADPH.Indan-1-ol + NAD(P)+ = indanone + NAD(P)H.
Enzyme regulation: Strongly inhibited by nonsteroidal anti-inflammatory drugs (NSAID) including flufenamic acid and indomethacin. Also inhibited by the flavinoid, rutin, and by selective serotonin inhibitors (SSRIs).
Subcellular location: Cytoplasm.
Tissue specificity: Expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. The dominant HSD in prostate and mammary gland. In the prostate, higher levels in epithelial cells than in stromal cells. In the brain, expressed in medulla, spinal cord, frontotemporal lobes, thalamus, subthalamic nuclei and amygdala. Weaker expression in the hippocampus, substantia nigra and caudate. Ref.2 Ref.4 Ref.5 Ref.6 Ref.8 Ref.14
Sequence similarities: Belongs to the aldo/keto reductase family.
Biophysicochemical propertiesKinetic parameters:KM=142.1 µM for progesterone Ref.6KM=2.37 µM for 5-alpha-dihydrotestosteroneKM=1.0 µM for androstanediolVmax=20.1 nmol/min/mg enzyme with progesterone as substrateVmax=1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as substrateVmax=4.4 nmol/min/mg enzyme with androstanediol as substrate
Sequence caution: The sequence BAA04619.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
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