Human 3-Oxo-5-Beta-Steroid 4-Dehydrogenase (AKR1D1) Protein

Background

AKR1D1, also known as Δ4-3-ketosteroid-5β-reductase, is a liver-specific enzyme that plays a pivotal role in bile acid synthesis and steroid hormone metabolism. It catalyzes the reduction of double bonds in Δ4-3-ketosteroids, converting cortisol, aldosterone, and other steroid precursors into their inactive 5β-reduced metabolites. This activity is essential for bile acid production, as AKR1D1 mediates the transformation of cholesterol-derived intermediates into bile acids, which are critical for lipid digestion and cholesterol homeostasis. AKR1D1 deficiency results in bile acid synthesis disorders, leading to cholestasis, liver dysfunction, and fat malabsorption. Additionally, AKR1D1 contributes to steroid clearance and inactivates glucocorticoids, regulating cortisol levels and preventing glucocorticoid excess. Dysregulation of AKR1D1 is linked to liver diseases, such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis, where impaired bile acid synthesis disrupts lipid metabolism. It is also implicated in metabolic syndrome and hormone-driven disorders due to its role in steroid hormone regulation.