Aldo-keto reductase family 1 member D1 (AKR1D1) (AKR1D1)

Aldo-keto reductase family 1 member D1 (AKR1D1), commonly referred to as 5β-reductase, is a hepatic enzyme that plays a pivotal role in both bile acid synthesis and the systemic clearance of steroid hormones [UniProt, NIH]. It is the only human enzyme capable of performing the stereospecific 5β-reduction of Δ4-3-ketosteroids, a structural modification that creates a 90-degree bend in the steroid nucleus, which is essential for the detergent-like properties of primary bile acids [PubMed]. In addition to its role in bile acid production, AKR1D1 is responsible for the inactivation of potent glucocorticoids and androgens, such as cortisol and testosterone, thereby modulating their availability for receptor binding [GeneCards]. Genetic defects in the AKR1D1 gene cause 5β-reductase deficiency, a condition that manifests as severe neonatal cholestasis and liver damage due to the accumulation of toxic bile acid intermediates [NIH]. This deficiency is effectively managed with oral primary bile acid replacement therapy, which restores bile flow and suppresses the production of hepatotoxic precursors [PubMed]. Emerging research also suggests that AKR1D1 dysregulation contributes to the development of metabolic disorders like non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, positioning the enzyme as a potential target for future metabolic therapies [PubMed].

Other names

3-oxo-5-beta-steroid 4-dehydrogenaseDelta(4)-3-ketosteroid 5-beta-reductaseSRD5B1CBAS23o5bred5-beta-reductaseSteroid 5-beta-reductase

Bile acid replacement therapy; Enzyme inhibition; Steroid metabolism modulation