DCXR Human

Dicarbonyl/L-Xylulose Reductase (DCXR), also known as carbonyl reductase II, is an enzyme encoded by the DCXR gene located on chromosome 17q25.3 in humans . This enzyme plays a crucial role in carbohydrate metabolism, glucose metabolism, and the uronate cycle . It is involved in the reduction of various sugars and alpha-dicarbonyl compounds, contributing to cellular osmoregulation and water absorption in the proximal renal tubules by producing xylitol .

The DCXR gene encodes a membrane protein that is approximately 34 kDa in size and composed of 224 amino acids . The protein is highly expressed in the kidney and localizes to the cytoplasmic membrane . The enzyme functions as a homotetramer with NADPH-linked reductase activity for both alpha-dicarbonyl compounds and L-xylulose .

DCXR catalyzes the reduction of L-xylulose to xylitol using NADPH as a cofactor . This reaction is part of the uronate cycle, which is essential for the metabolism of pentoses, tetroses, and trioses . The enzyme also reduces various alpha-dicarbonyl compounds, which are toxic byproducts of cellular metabolism . By converting these compounds into less harmful substances, DCXR helps protect cells from oxidative stress and damage .

A deficiency in DCXR activity can lead to a rare metabolic disorder known as pentosuria, characterized by the excessive excretion of L-xylulose in the urine . This condition is generally benign but can be mistaken for diabetes due to the presence of reducing sugars in the urine . Additionally, overexpression of DCXR has been associated with prostate adenocarcinoma, suggesting a potential role in cancer progression .

Recent studies have identified DCXR as a potential therapeutic target for chronic kidney disease (CKD) . Lower expression of DCXR in renal tissue has been associated with more severe disease and worse outcomes in CKD patients . Enhancing DCXR expression or activity could offer a novel approach to mitigating the progression of CKD and improving patient outcomes .