Aldo-keto reductase family 1 member C4 (AKR1C4)

Aldo-keto reductase family 1 member C4 (AKR1C4) is a liver-specific enzyme belonging to the aldo-keto reductase superfamily[2][3]. It primarily catalyzes NAD(P)H-dependent reductions of ketosteroids, including the conversion of 3-ketosteroids to 3α-hydroxysteroids, and plays essential roles in steroid hormone metabolism, bile acid synthesis, and detoxification processes[2][3][4]. AKR1C4 also catalyzes the reduction of xenobiotics such as chlordecone[2][3]. Overexpression of AKR1C4 and other family members has been implicated in cancer malignancy and chemoresistance[4]. It is known for metabolic inactivation of anthracycline class chemotherapeutics (e.g., doxorubicin), impacting their clinical efficacy[4]. The enzyme’s high sequence similarity and functional overlap with other AKR1C isoforms create challenges for developing specific inhibitors[4].

Other names

3α-Hydroxysteroid dehydrogenase type 13α-HSD1CDRChlordecone reductaseDD4HAKRADihydrodiol dehydrogenase 4CHDR3alpha-hydroxysteroid 3-dehydrogenase3-alpha-HSD1

Enzyme substrate reduction: catalyzes the conversion of oxidized steroid intermediates (e.g., reduces ketosteroids to hydroxysteroids using NADPH/NADH) - Inactivation of chemotherapeutic drugs via carbonyl reduction (e.g., doxorubicin to less active alcohol metabolite)