DCXR

Official Full Name

dicarbonyl and L-xylulose reductase

Organism

Homo sapiens

GeneID

51181

Background

The protein encoded by this gene acts as a homotetramer to catalyze diacetyl reductase and L-xylulose reductase reactions. The encoded protein may play a role in the uronate cycle of glucose metabolism and in the cellular osmoregulation in the proximal renal tubules. Defects in this gene are a cause of pentosuria. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

Synonyms

XR; DCR; HCR2; P34H; HCRII; KIDCR; PNTSU; SDR20C1;

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Detailed Information

The dicarbonyl/L-xylulose reductase (DCXR) gene, also known as D-xylulose reductase or aldo-keto reductase (AKR) 1B1, is an enzyme encoded by the DCXR gene. This enzyme belongs to the aldo-keto reductase family, which is a group of enzymes that catalyze the reduction of various aldehydes and ketones to their corresponding alcohols. The DCXR enzyme is particularly known for its role in the metabolism of xylulose, a hexose that is an important intermediate in the metabolic pathways of many organisms, including bacteria, yeast, and plants.

Structure of DCXR

The DCXR enzyme is a member of the aldo-keto reductase family, which is characterized by a conserved catalytic core domain containing a highly conserved N-terminal cysteine, which is involved in the binding of the substrate. The enzyme has a characteristic Rossmann-fold structure that binds the substrate and facilitates the reduction reaction. The DCXR enzyme specifically catalyzes the reduction of xylulose to L-xylose, utilizing NAD(P)H as the cofactor. The enzyme has a Km value of approximately 100 μM for xylulose and a pH optima of around 7.5-8.0.

Function of DCXR

The DCXR enzyme is involved in various metabolic pathways, including the xylose metabolism pathway in bacteria and yeast, the polyol pathway in plants, and the glycerolipid metabolism in animals. In bacteria and yeast, the DCXR enzyme plays a crucial role in the utilization of xylose, which is a major component of plant cell walls. The enzyme is involved in the conversion of xylose to L-xylose, which is further metabolized to produce energy or used in the synthesis of various biochemicals. In plants, the DCXR enzyme is involved in the polyol pathway, where it reduces xylose to L-xylose, which is then converted to other polyols such as sorbitol and mannitol. In animals, the DCXR enzyme is involved in the glycerolipid metabolism, where it plays a role in the synthesis and breakdown of glycerolipids.

Figure 1. Functional implications of DCXR.

Implications of DCXR in Diseases

Research on the DCXR gene and its encoded enzyme has revealed its involvement in various physiological and pathological processes. In recent years, the enzyme has gained attention for its potential role in the development and progression of various diseases, including diabetes, obesity, and cancer.

Diabetes is a metabolic disorder characterized by hyperglycemia, which can lead to various complications such as neuropathy, nephropathy, and retinopathy. The DCXR enzyme has been found to be upregulated in diabetes, where it plays a role in the conversion of xylose to L-xylose, which is then used in the synthesis of polyols. Increased levels of polyols have been associated with diabetic complications, suggesting that the DCXR enzyme may contribute to the development of diabetes and its complications.

Obesity is a global health issue that has been linked to various metabolic disorders, including diabetes and cardiovascular diseases. Research has shown that the DCXR enzyme is upregulated in obese individuals, where it plays a role in the synthesis of fatty acids and triacylglycerols. Increased levels of fatty acids and triacylglycerols have been associated with obesity and the development of metabolic syndrome, suggesting that the DCXR enzyme may contribute to the pathogenesis of obesity and related metabolic disorders.

Cancer is a leading cause of death worldwide, and its development has been linked to various factors, including oxidative stress and inflammation. Recent studies have shown that the DCXR enzyme is upregulated in various cancer types, where it plays a role in the reduction of reactive oxygen species (ROS) and other aldehydes. Increased levels of ROS have been associated with cancer development and progression, suggesting that the DCXR enzyme may contribute to the pathogenesis of cancer and its related complications.

References:

Lee, Sun-Kyung et al. "Dicarbonyl/l-xylulose reductase (DCXR): The multifunctional pentosuria enzyme." The international journal of biochemistry & cell biology vol. 45,11 (2013): 2563-7. doi:10.1016/j.biocel.2013.08.010
Kim, Yuh-Nam et al. "Dicarbonyl/L-xylulose reductase (DCXR) producing xylitol regulates egg retention through osmolality control in Caenorhabditis elegans." Animal cells and systems vol. 26,5 223-231. 6 Oct. 2022, doi:10.1080/19768354.2022.2126886

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