Aldo-keto reductase family 1 (AKR1)

Aldo-keto reductase family 1 (AKR1) comprises a group of cytosolic, monomeric NAD(P)(H)-dependent oxidoreductases involved in the reduction of aldehydes and ketones to their corresponding alcohols[1][2][4][6]. This enzyme family metabolizes a broad range of endogenous and exogenous carbonyl-containing compounds, including steroids, prostaglandins, retinoids, and xenobiotics, playing essential roles in steroid hormone metabolism, detoxification, and intermediary metabolism[1][2][4]. Members of AKR1 such as AKR1B1 (aldose reductase) and AKR1C isoforms (AKR1C1-4) have been directly implicated in the pathogenesis of diseases like diabetes complications and hormone-driven cancers[1][2]. Inhibitors of AKR1 enzymes are in development and use for therapeutic intervention in diabetic complications and some cancers[1][2]. The AKR1 proteins share a characteristic (α/β)_8-barrel fold and conserved catalytic tetrad, with substrate specificity dictated by loop regions modifying the enzyme active site[1][7].

Other names

Aldo-keto reductase 1AKR1AKR1C (family)AKR1B1 (aldose reductase)AKR1C1AKR1C2AKR1C3AKR1C4steroid 5β-reductase (AKR1D1)dihydrodiol dehydrogenase

Inhibition of enzyme catalytic activity (competitive or allosteric inhibition); Modulation of steroid hormone metabolism; Alteration of prostaglandin synthesis pathways