AKR1C1

Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids. Displays broad substrate specificity with distinct positional and stereochemistry, primarily generating 20alpha-hydroxysteroids, but also 3alpha/beta- and 17beta-hydroxysteroids. Involved in neurosteroid metabolism. Reduces 5alpha-dihydrodeoxycorticosterone (5-alpha-DHDOC) to neuroactive steroid 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) known to alter neural excitability via allosteric activation of gamma-aminobutyric acid type A (GABAAR) receptors. Inactivates 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) into less potent neurosteroid 3alpha,20alpha-dihydroxy-5alpha-pregnane. Catalyzes the reduction of progesterone to less potent progestogen (20S)-hydroxypregn-4-en-3-one likely regulating ligand availability for progesterone receptors. In androgen catabolism, may predominantly act as a phase I enzyme by introducing a hydroxyl group prior to conjugation. It can nevertheless participate in the alternative phase II pathway by directly reducing sulfate- or glucuronide-conjugated androgens. In vitro can efficiently catalyze bidirectional conversion between ketosteroids and hydroxysteroids using NADPH/NADP(+) or NADH/NAD(+) as cofactors. In vivo however, the reductase activity prevails since the major reducing cofactor NADPH inhibits NAD(+)-dependent oxidase activity..

Function from UniProtKB (Q04828), read 2026-09-23. CC BY 4.0.