aldo-keto reductase family 1 member C3; prostaglandin F synthase; PGFS; trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; 3-alpha-hydroxysteroid dehydrogenase type 2; 3-alpha-HSD type 2; 3-alpha-HSD type II, brain; testosterone 17-beta-dehydrogenase 5; 17-beta-hydroxysteroid dehydrogenase type 5; 17-beta-HSD 5; dihydrodiol dehydrogenase type I; dihydrodiol dehydrogenase 3; DD-3; DD3; chlordecone reductase homolog HAKRb; HA1753 (AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS)

Function

• catalyzes the conversion of aldehydes & ketones to alcohols
• catalyzes reduction of prostaglandin PGD2, PGH2 & phenanthrenequinone & oxidation of 9-alpha,11-beta-PGF2 to PGD2
• functions as a bi-directional 3-alpha-, 17-beta- & 20-alpha hydroxysteroid dehydrogenase
• dominant hydroxysteroid dehydrogenase in prostate & mammary gland
• can interconvert active androgens, estrogens & progestins with their cognate inactive metabolites
• preferentially transforms androstenedione (4-dione) to testosterone
• strongly inhibited by nonsteroidal anti-inflammatory drugs including flufenamic acid & indomethacin
• also inhibited by the flavinoid, rutin, & by selective serotonin inhibitors (SSRIs)

Kinetic parameters:

• KM=142.1 uM for progesterone
• KM=2.37 uM for 5-alpha-dihydrotestosterone
• KM=1.0 uM for androstanediol
• Vmax=20.1 nmol/min/mg enzyme with progesterone as substrate
• Vmax=1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as substrate
• Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate

trans-1,2-dihydrobenzene-1,2-diol + NADP+ <--> catechol + NADPH ;
androsterone + NAD+/NADP+
           <-->
5-alpha-androstane-3,17-dione + NADH/NADPH

(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+ <--> androst-4-ene-3,17-dione + NADH

testosterone + NADP+ <--> androst-4-ene-3,17-dione + NADPH

Structure

belongs to the aldo/keto reductase family

Compartment

cytoplasm

Expression

• expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate & testis
• 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 & amygdala; weaker expression in the hippocampus, substantia nigra & caudate

More general terms

• trans-1,2-dihydrobenzene-1,2-diol dehydrogenase

Database

• UniProt: http://www.uniprot.org/uniprot/P42330.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8644
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8644
• OMIM: https://mirror.omim.org/entry/603966