Aldo-Keto Reductase Family 1 Member D1 (AKR1D1) is a crucial enzyme in human biochemistry, playing a significant role in the metabolism of bile acids and steroid hormones. This enzyme is part of the larger aldo-keto reductase (AKR) superfamily, which is involved in the reduction of aldehydes and ketones to their corresponding alcohols.
The AKR1D1 gene is located on chromosome 7 and encodes a protein that is approximately 37 kDa in size . The enzyme is also known by several other names, including Delta(4)-3-Ketosteroid 5-Beta-Reductase and Steroid-5-Beta-Reductase, Beta Polypeptide 1 . The protein structure includes a NADPH-binding domain, which is essential for its reductase activity.
AKR1D1 catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of bile acid intermediates and steroid hormones carrying a delta (4)-3-one structure . This reaction is crucial for the biosynthesis of bile acids, which are essential for the digestion and absorption of dietary fats. The enzyme’s activity also plays a significant role in steroid metabolism, converting steroid hormones into their active or inactive forms .
The enzyme’s activity is vital for maintaining normal liver function and overall metabolic homeostasis. Deficiency in AKR1D1 can lead to various metabolic disorders, including bile acid synthesis defects and hepatic dysfunction . Additionally, mutations in the AKR1D1 gene have been associated with neonatal cholestasis, hepatitis, and liver failure .
Given its crucial role in bile acid and steroid hormone metabolism, AKR1D1 is a potential target for therapeutic interventions in metabolic and liver diseases. Research is ongoing to develop inhibitors or activators of AKR1D1 that could be used to treat conditions resulting from its deficiency or overactivity .
Human recombinant AKR1D1 is produced using recombinant DNA technology, which involves inserting the human AKR1D1 gene into a suitable expression system, such as bacteria or yeast. This allows for the large-scale production of the enzyme for research and therapeutic purposes. Recombinant AKR1D1 is used in various biochemical assays to study its function and to screen for potential therapeutic compounds .